General Information:

Id: 4,462
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mus musculus
male
article
Reference: Liu C et al.(2007) Transcriptional coactivator PGC-1alpha integrates the mammalian clock and energy metabolism Nature 7143: 477-481 [PMID: 17476214]

Interaction Information:

Comment To determine the effects of PGC-1alpha on clock genes, primary hepatocytes and C2C12 myotubes were transduced with recombinant adenoviruses expressing green fluorescent protein (GFP) or PGC-1alpha. Quantitative PCR analyses indicate that PGC-1alpha induces the expression of Bmal1 and Clock in both cell types. Consistent with messenger RNA expression, Bmal1 and Clock protein levels are elevated in hepatocytes in response to PGC-1alpha. Clock and Bmal1 are two basic helix-loop-helix transcription factors that activate the transcription of period (Per) and cryptochrome (Cry) genes.
Formal Description
Interaction-ID: 44965

gene/protein

PPARGC1A

increases_expression of

gene/protein

ARNTL

Comment To determine the effects of PGC-1alpha on clock genes, primary hepatocytes and C2C12 myotubes were transduced with recombinant adenoviruses expressing green fluorescent protein (GFP) or PGC-1alpha. Quantitative PCR analyses indicate that PGC-1alpha induces the expression of Bmal1 and Clock in both cell types. Consistent with messenger RNA expression, Bmal1 and Clock protein levels are elevated in hepatocytes in response to PGC-1alpha. Clock and Bmal1 are two basic helix-loop-helix transcription factors that activate the transcription of period (Per) and cryptochrome (Cry) genes.
Formal Description
Interaction-ID: 45299

gene/protein

PPARGC1A

increases_expression of

gene/protein

CLOCK

Comment Although PGC-1alpha exerts only modest effects on the expression of RORalpha (Rora) and RORgamma (Rorc), it significantly induces Rev-erbalpha and Rev-erbbeta expression.
Formal Description
Interaction-ID: 45300

gene/protein

PPARGC1A

increases_expression of

gene/protein

NR1D1

Comment Although PGC-1alpha exerts only modest effects on the expression of RORalpha (Rora) and RORgamma (Rorc), it significantly induces Rev-erbalpha and Rev-erbbeta expression.
Formal Description
Interaction-ID: 45301

gene/protein

PPARGC1A

increases_expression of

gene/protein

NR1D2

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45302

gene/protein

PPARGC1A

increases_expression of

gene/protein

USP2

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45303

gene/protein

PPARGC1A

increases_expression of

gene/protein

ATP1A1

Drugbank entries Show/Hide entries for ATP1A1
Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45304

gene/protein

PPARGC1A

increases_expression of

gene/protein

CIDEB

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45305

gene/protein

PPARGC1A

increases_expression of

gene/protein

ACO2

Drugbank entries Show/Hide entries for ACO2
Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45306

gene/protein

PPARGC1A

increases_expression of

gene/protein

ALAS1

Drugbank entries Show/Hide entries for ALAS1
Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45307

gene/protein

PPARGC1A

increases_expression of

gene/protein

UPP2

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45308

gene/protein

PPARGC1A

increases_expression of

gene/protein

DMD

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45309

gene/protein

PPARGC1A

increases_expression of

gene/protein

SLC2A2

Drugbank entries Show/Hide entries for SLC2A2
Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45310

gene/protein

PPARGC1A

increases_expression of

gene/protein

HIST1H2BC

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45311

gene/protein

PPARGC1A

increases_expression of

gene/protein

NDRG2

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45312

gene/protein

PPARGC1A

increases_expression of

gene/protein

GABARAPL1

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45313

gene/protein

PPARGC1A

increases_expression of

gene/protein

NDUFAF4

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45314

gene/protein

PPARGC1A

increases_expression of

gene/protein

ARSA

Drugbank entries Show/Hide entries for ARSA
Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45315

gene/protein

PPARGC1A

increases_expression of

gene/protein

ELOVL6

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45316

gene/protein

PPARGC1A

increases_expression of

gene/protein

ID2

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45317

gene/protein

PPARGC1A

increases_expression of

gene/protein

G0S2

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45318

gene/protein

PPARGC1A

increases_expression of

gene/protein

Uox

this gene is nonfunctional in humans
Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45319

gene/protein

PPARGC1A

increases_expression of

gene/protein

CLK4

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45320

gene/protein

PPARGC1A

increases_expression of

gene/protein

SAR1B

Drugbank entries Show/Hide entries for SAR1B
Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45321

gene/protein

PPARGC1A

increases_expression of

gene/protein

CPT1A

Drugbank entries Show/Hide entries for CPT1A
Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45322

gene/protein

PPARGC1A

increases_expression of

gene/protein

Cyp3a25

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45323

gene/protein

PPARGC1A

increases_expression of

gene/protein

PER2

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45324

gene/protein

PPARGC1A

increases_expression of

gene/protein

MRPL20

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45325

gene/protein

PPARGC1A

increases_expression of

gene/protein

CEBPB

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45326

gene/protein

PPARGC1A

increases_expression of

gene/protein

PDHB

Drugbank entries Show/Hide entries for PDHB
Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45327

gene/protein

PPARGC1A

increases_expression of

gene/protein

LPIN1

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45329

gene/protein

PPARGC1A

increases_expression of

gene/protein

PAH

Drugbank entries Show/Hide entries for PAH
Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45330

gene/protein

PPARGC1A

increases_expression of

gene/protein

CRIP2

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45332

gene/protein

PPARGC1A

increases_expression of

gene/protein

Timm8a1

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45333

gene/protein

PPARGC1A

increases_expression of

gene/protein

Tgoln1

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45334

gene/protein

PPARGC1A

increases_expression of

gene/protein

TRIM41

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45336

gene/protein

PPARGC1A

increases_expression of

gene/protein

ORMDL3

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45337

gene/protein

PPARGC1A

increases_expression of

gene/protein

MRPS21

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45338

gene/protein

PPARGC1A

increases_expression of

gene/protein

GLRX

Drugbank entries Show/Hide entries for GLRX
Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45339

gene/protein

PPARGC1A

increases_expression of

gene/protein

FLNB

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45340

gene/protein

PPARGC1A

increases_expression of

gene/protein

TMEM14C

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45341

gene/protein

PPARGC1A

increases_expression of

gene/protein

Cyp4a12

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45342

gene/protein

PPARGC1A

increases_expression of

gene/protein

Cyp2a12

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45343

gene/protein

PPARGC1A

increases_expression of

gene/protein

ALDOB

Drugbank entries Show/Hide entries for ALDOB
Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45344

gene/protein

PPARGC1A

increases_expression of

gene/protein

LONP1

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45345

gene/protein

PPARGC1A

increases_expression of

gene/protein

PHYH

Drugbank entries Show/Hide entries for PHYH
Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45346

gene/protein

PPARGC1A

increases_expression of

gene/protein

MFF

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45347

gene/protein

PPARGC1A

increases_expression of

gene/protein

MCFD2

Drugbank entries Show/Hide entries for MCFD2
Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45348

gene/protein

PPARGC1A

increases_expression of

gene/protein

HSPE1

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45349

gene/protein

PPARGC1A

increases_expression of

gene/protein

ATL2

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45350

gene/protein

PPARGC1A

increases_expression of

gene/protein

HSPD1

Comment To assess the role of PGC-1alpha in the regulation of circadian gene expression at the transcriptome level, microarray analysis was performed on total RNA isolated from primary hepatocytes transduced with GFP or PGC-1alpha adenoviruses. 47 of the circadian-regulated genes are induced by PGC-1alpha by more than 1.8-fold, with the expression of many clustering at the onset and during early dark phase.
Formal Description
Interaction-ID: 45351

gene/protein

PPARGC1A

increases_expression of

gene/protein

TFPI2

Comment Analysis of PGC-1alpha mRNA levels in mouse liver revealed a diurnal rhythm that peaks at CT13 (CT0 is the onset at hour 0 of subjective light period), gradually declines thereafter, and reaches a nadir at CT1. PGC-1alpha expression is similarly rhythmic in skeletal muscle, though to a lesser degree. The expression of other PGC-1 coactivators, that is, PGC-1beta and PRC, also show circadian rhythms in these tissues.
Formal Description
Interaction-ID: 45352

affects_expression of

gene/protein

PPARGC1A

in liver, in skeletal muscle
Comment Analysis of PGC-1alpha mRNA levels in mouse liver revealed a diurnal rhythm that peaks at CT13 (CT0 is the onset at hour 0 of subjective light period), gradually declines thereafter, and reaches a nadir at CT1. PGC-1alpha expression is similarly rhythmic in skeletal muscle, though to a lesser degree. The expression of other PGC-1 coactivators, that is, PGC-1beta and PRC, also show circadian rhythms in these tissues.
Formal Description
Interaction-ID: 45357

affects_expression of

gene/protein

PPARGC1B

in liver, in skeletal muscle
Comment Analysis of PGC-1alpha mRNA levels in mouse liver revealed a diurnal rhythm that peaks at CT13 (CT0 is the onset at hour 0 of subjective light period), gradually declines thereafter, and reaches a nadir at CT1. PGC-1alpha expression is similarly rhythmic in skeletal muscle, though to a lesser degree. The expression of other PGC-1 coactivators, that is, PGC-1beta and PRC, also show circadian rhythms in these tissues.
Formal Description
Interaction-ID: 45358

affects_expression of

gene/protein

PPRC1

in liver, in skeletal muscle
Comment To identify transcription factors that mediate the regulation of clock genes by PGC-1alpha, the ability of PGC-1alpha to synergize with these factors in the regulation of Bmal1 transcription was examined. PGC-1alpha dramatically augments the transcriptional activity of RORalpha and RORgamma, but not C/EBPalpha, on a Bmal1 promoter reporter. Coactivation of RORalpha by PGC-1alpha was previously observed for genes involved in muscle lipid metabolism. In contrast, PGC-1alpha exerts modest effects on the transcriptional activity of Clock/Bmal1. The synergistic effects of ROR and PGC-1alpha are abolished when the ROR-binding sites (RORE) on the proximal Bmal1 promoter are mutated. Physical interaction assays indicate that PGC-1alpha binds to RORalpha and RORgamma through the LXXLL motifs. Previous studies indicate that Rev-erbalpha negatively regulates Bmal1 transcription by recruiting corepressor proteins, indicating that the induction of Rev-erb factors may provide a negative feedback mechanism for PGC-1alpha function. These results illustrate that the ability of PGC-1alpha to activate Bmal1 transcription is modulated by the relative abundance of the ROR and Rev-erb families of orphan receptors.
Formal Description
Interaction-ID: 45359

gene/protein

PPARGC1A

increases_activity of

gene/protein

RORA

Drugbank entries Show/Hide entries for RORA
Comment To identify transcription factors that mediate the regulation of clock genes by PGC-1alpha, the ability of PGC-1alpha to synergize with these factors in the regulation of Bmal1 transcription was examined. PGC-1alpha dramatically augments the transcriptional activity of RORalpha and RORgamma, but not C/EBPalpha, on a Bmal1 promoter reporter. Coactivation of RORalpha by PGC-1alpha was previously observed for genes involved in muscle lipid metabolism. In contrast, PGC-1alpha exerts modest effects on the transcriptional activity of Clock/Bmal1. The synergistic effects of ROR and PGC-1alpha are abolished when the ROR-binding sites (RORE) on the proximal Bmal1 promoter are mutated. Physical interaction assays indicate that PGC-1alpha binds to RORalpha and RORgamma through the LXXLL motifs. Previous studies indicate that Rev-erbalpha negatively regulates Bmal1 transcription by recruiting corepressor proteins, indicating that the induction of Rev-erb factors may provide a negative feedback mechanism for PGC-1alpha function. These results illustrate that the ability of PGC-1alpha to activate Bmal1 transcription is modulated by the relative abundance of the ROR and Rev-erb families of orphan receptors.
Formal Description
Interaction-ID: 45360

gene/protein

PPARGC1A

increases_activity of

gene/protein

RORC

Comment To identify transcription factors that mediate the regulation of clock genes by PGC-1alpha, the ability of PGC-1alpha to synergize with these factors in the regulation of Bmal1 transcription was examined. PGC-1alpha dramatically augments the transcriptional activity of RORalpha and RORgamma, but not C/EBPalpha, on a Bmal1 promoter reporter. Coactivation of RORalpha by PGC-1alpha was previously observed for genes involved in muscle lipid metabolism. In contrast, PGC-1alpha exerts modest effects on the transcriptional activity of Clock/Bmal1. The synergistic effects of ROR and PGC-1alpha are abolished when the ROR-binding sites (RORE) on the proximal Bmal1 promoter are mutated. Physical interaction assays indicate that PGC-1alpha binds to RORalpha and RORgamma through the LXXLL motifs. Previous studies indicate that Rev-erbalpha negatively regulates Bmal1 transcription by recruiting corepressor proteins, indicating that the induction of Rev-erb factors may provide a negative feedback mechanism for PGC-1alpha function. These results illustrate that the ability of PGC-1alpha to activate Bmal1 transcription is modulated by the relative abundance of the ROR and Rev-erb families of orphan receptors.
Formal Description
Interaction-ID: 45361

gene/protein

PPARGC1A

NOT increases_activity of

gene/protein

CEBPA

Comment PGC-1alpha regulates locomotor behaviour in mice and is required for maintaining normal circadian periods.
Formal Description
Interaction-ID: 45362

gene/protein

PPARGC1A

affects_activity of

Comment PGC-1alpha regulates locomotor behaviour in mice and is required for maintaining normal circadian periods.
Formal Description
Interaction-ID: 45363

gene/protein

PPARGC1A

affects_activity of

Comment PEPCK (PCK1), a rate-limiting enzyme of hepatic gluconeogenesis, shows a daily cycle that peaks at CT13 in the wild-type liver. PGC-1alpha seems to be dispensable for the rhythmic expression of this enzyme. Nevertheless, the mRNA levels of PEPCK are constitutively elevated at CT1 and CT13, in a similar way to the previous studies. Pyruvate dehydrogenase kinase 4 (PDK4) is a key regulator of the pyruvate dehydrogenase complex that controls the flux of pyruvate into the tricarboxylic acid cycle. The diurnal PDK4 expression is severely impaired in PGC-1alpha-deficient liver and skeletal muscle, although the phase of PDK4 oscillation seems to be preserved. Similarly, the cyclic expression of fatty acid binding protein 3 (Fabp3/H-FABP) as well as other mitochondrial genes involved in oxidative phosphorylation (OXPHOS), such as aconitase (Aco2) and Cox4a (Cox4i1), is also disrupted in PGC-1alpha null skeletal muscle. Together, the results illustrate that PGC-1alpha is essential for oscillatory expression of clock and metabolic genes in vivo.
Formal Description
Interaction-ID: 45364

affects_expression of

gene/protein

PCK1

in liver; independent of PPARGC1A
Drugbank entries Show/Hide entries for PCK1
Comment PEPCK (PCK1), a rate-limiting enzyme of hepatic gluconeogenesis, shows a daily cycle that peaks at CT13 in the wild-type liver. PGC-1alpha seems to be dispensable for the rhythmic expression of this enzyme. Nevertheless, the mRNA levels of PEPCK are constitutively elevated at CT1 and CT13, in a similar way to the previous studies. Pyruvate dehydrogenase kinase 4 (PDK4) is a key regulator of the pyruvate dehydrogenase complex that controls the flux of pyruvate into the tricarboxylic acid cycle. The diurnal PDK4 expression is severely impaired in PGC-1alpha-deficient liver and skeletal muscle, although the phase of PDK4 oscillation seems to be preserved. Similarly, the cyclic expression of fatty acid binding protein 3 (Fabp3/H-FABP) as well as other mitochondrial genes involved in oxidative phosphorylation (OXPHOS), such as aconitase (Aco2) and Cox4a (Cox4i1), is also disrupted in PGC-1alpha null skeletal muscle. Together, the results illustrate that PGC-1alpha is essential for oscillatory expression of clock and metabolic genes in vivo.
Formal Description
Interaction-ID: 45365

affects_expression of

gene/protein

PDK4

via PPARGC1A
Drugbank entries Show/Hide entries for PDK4
Comment PEPCK (PCK1), a rate-limiting enzyme of hepatic gluconeogenesis, shows a daily cycle that peaks at CT13 in the wild-type liver. PGC-1alpha seems to be dispensable for the rhythmic expression of this enzyme. Nevertheless, the mRNA levels of PEPCK are constitutively elevated at CT1 and CT13, in a similar way to the previous studies. Pyruvate dehydrogenase kinase 4 (PDK4) is a key regulator of the pyruvate dehydrogenase complex that controls the flux of pyruvate into the tricarboxylic acid cycle. The diurnal PDK4 expression is severely impaired in PGC-1alpha-deficient liver and skeletal muscle, although the phase of PDK4 oscillation seems to be preserved. Similarly, the cyclic expression of fatty acid binding protein 3 (Fabp3/H-FABP) as well as other mitochondrial genes involved in oxidative phosphorylation (OXPHOS), such as aconitase (Aco2) and Cox4a (Cox4i1), is also disrupted in PGC-1alpha null skeletal muscle. Together, the results illustrate that PGC-1alpha is essential for oscillatory expression of clock and metabolic genes in vivo.
Formal Description
Interaction-ID: 45366

affects_expression of

gene/protein

FABP3

via PPARGC1A
Comment PEPCK (PCK1), a rate-limiting enzyme of hepatic gluconeogenesis, shows a daily cycle that peaks at CT13 in the wild-type liver. PGC-1alpha seems to be dispensable for the rhythmic expression of this enzyme. Nevertheless, the mRNA levels of PEPCK are constitutively elevated at CT1 and CT13, in a similar way to the previous studies. Pyruvate dehydrogenase kinase 4 (PDK4) is a key regulator of the pyruvate dehydrogenase complex that controls the flux of pyruvate into the tricarboxylic acid cycle. The diurnal PDK4 expression is severely impaired in PGC-1alpha-deficient liver and skeletal muscle, although the phase of PDK4 oscillation seems to be preserved. Similarly, the cyclic expression of fatty acid binding protein 3 (Fabp3/H-FABP) as well as other mitochondrial genes involved in oxidative phosphorylation (OXPHOS), such as aconitase (Aco2) and Cox4a (Cox4i1), is also disrupted in PGC-1alpha null skeletal muscle. Together, the results illustrate that PGC-1alpha is essential for oscillatory expression of clock and metabolic genes in vivo.
Formal Description
Interaction-ID: 45367

affects_expression of

gene/protein

ACO2

via PPARGC1A
Drugbank entries Show/Hide entries for ACO2
Comment PEPCK (PCK1), a rate-limiting enzyme of hepatic gluconeogenesis, shows a daily cycle that peaks at CT13 in the wild-type liver. PGC-1alpha seems to be dispensable for the rhythmic expression of this enzyme. Nevertheless, the mRNA levels of PEPCK are constitutively elevated at CT1 and CT13, in a similar way to the previous studies. Pyruvate dehydrogenase kinase 4 (PDK4) is a key regulator of the pyruvate dehydrogenase complex that controls the flux of pyruvate into the tricarboxylic acid cycle. The diurnal PDK4 expression is severely impaired in PGC-1alpha-deficient liver and skeletal muscle, although the phase of PDK4 oscillation seems to be preserved. Similarly, the cyclic expression of fatty acid binding protein 3 (Fabp3/H-FABP) as well as other mitochondrial genes involved in oxidative phosphorylation (OXPHOS), such as aconitase (Aco2) and Cox4a (Cox4i1), is also disrupted in PGC-1alpha null skeletal muscle. Together, the results illustrate that PGC-1alpha is essential for oscillatory expression of clock and metabolic genes in vivo.
Formal Description
Interaction-ID: 45368

affects_expression of

gene/protein

COX4I1

via PPARGC1A
Drugbank entries Show/Hide entries for COX4I1
Comment PEPCK (PCK1), a rate-limiting enzyme of hepatic gluconeogenesis, shows a daily cycle that peaks at CT13 in the wild-type liver. PGC-1alpha seems to be dispensable for the rhythmic expression of this enzyme. Nevertheless, the mRNA levels of PEPCK are constitutively elevated at CT1 and CT13, in a similar way to the previous studies. Pyruvate dehydrogenase kinase 4 (PDK4) is a key regulator of the pyruvate dehydrogenase complex that controls the flux of pyruvate into the tricarboxylic acid cycle. The diurnal PDK4 expression is severely impaired in PGC-1alpha-deficient liver and skeletal muscle, although the phase of PDK4 oscillation seems to be preserved. Similarly, the cyclic expression of fatty acid binding protein 3 (Fabp3/H-FABP) as well as other mitochondrial genes involved in oxidative phosphorylation (OXPHOS), such as aconitase (Aco2) and Cox4a (Cox4i1), is also disrupted in PGC-1alpha null skeletal muscle. Together, the results illustrate that PGC-1alpha is essential for oscillatory expression of clock and metabolic genes in vivo.
Formal Description
Interaction-ID: 45369

affects_activity of

process

gluconeogenesis

via PCK1
Comment PEPCK (PCK1), a rate-limiting enzyme of hepatic gluconeogenesis, shows a daily cycle that peaks at CT13 in the wild-type liver. PGC-1alpha seems to be dispensable for the rhythmic expression of this enzyme. Nevertheless, the mRNA levels of PEPCK are constitutively elevated at CT1 and CT13, in a similar way to the previous studies. Pyruvate dehydrogenase kinase 4 (PDK4) is a key regulator of the pyruvate dehydrogenase complex that controls the flux of pyruvate into the tricarboxylic acid cycle. The diurnal PDK4 expression is severely impaired in PGC-1alpha-deficient liver and skeletal muscle, although the phase of PDK4 oscillation seems to be preserved. Similarly, the cyclic expression of fatty acid binding protein 3 (Fabp3/H-FABP) as well as other mitochondrial genes involved in oxidative phosphorylation (OXPHOS), such as aconitase (Aco2) and Cox4a (Cox4i1), is also disrupted in PGC-1alpha null skeletal muscle. Together, the results illustrate that PGC-1alpha is essential for oscillatory expression of clock and metabolic genes in vivo.
Formal Description
Interaction-ID: 45370

affects_activity of

complex/PPI

Pyruvate dehydrogenase complex

via PPARGC1A and PDK4
Comment PEPCK (PCK1), a rate-limiting enzyme of hepatic gluconeogenesis, shows a daily cycle that peaks at CT13 in the wild-type liver. PGC-1alpha seems to be dispensable for the rhythmic expression of this enzyme. Nevertheless, the mRNA levels of PEPCK are constitutively elevated at CT1 and CT13, in a similar way to the previous studies. Pyruvate dehydrogenase kinase 4 (PDK4) is a key regulator of the pyruvate dehydrogenase complex that controls the flux of pyruvate into the tricarboxylic acid cycle. The diurnal PDK4 expression is severely impaired in PGC-1alpha-deficient liver and skeletal muscle, although the phase of PDK4 oscillation seems to be preserved. Similarly, the cyclic expression of fatty acid binding protein 3 (Fabp3/H-FABP) as well as other mitochondrial genes involved in oxidative phosphorylation (OXPHOS), such as aconitase (Aco2) and Cox4a (Cox4i1), is also disrupted in PGC-1alpha null skeletal muscle. Together, the results illustrate that PGC-1alpha is essential for oscillatory expression of clock and metabolic genes in vivo.
Formal Description
Interaction-ID: 45371

gene/protein

PDK4

affects_activity of

complex/PPI

Pyruvate dehydrogenase complex

Drugbank entries Show/Hide entries for PDK4
Comment PEPCK (PCK1), a rate-limiting enzyme of hepatic gluconeogenesis, shows a daily cycle that peaks at CT13 in the wild-type liver. PGC-1alpha seems to be dispensable for the rhythmic expression of this enzyme. Nevertheless, the mRNA levels of PEPCK are constitutively elevated at CT1 and CT13, in a similar way to the previous studies. Pyruvate dehydrogenase kinase 4 (PDK4) is a key regulator of the pyruvate dehydrogenase complex that controls the flux of pyruvate into the tricarboxylic acid cycle. The diurnal PDK4 expression is severely impaired in PGC-1alpha-deficient liver and skeletal muscle, although the phase of PDK4 oscillation seems to be preserved. Similarly, the cyclic expression of fatty acid binding protein 3 (Fabp3/H-FABP) as well as other mitochondrial genes involved in oxidative phosphorylation (OXPHOS), such as aconitase (Aco2) and Cox4a (Cox4i1), is also disrupted in PGC-1alpha null skeletal muscle. Together, the results illustrate that PGC-1alpha is essential for oscillatory expression of clock and metabolic genes in vivo.
Formal Description
Interaction-ID: 45372

complex/PPI

Pyruvate dehydrogenase complex

affects_activity of

via PPARGC1A and PDK4
Comment PEPCK (PCK1), a rate-limiting enzyme of hepatic gluconeogenesis, shows a daily cycle that peaks at CT13 in the wild-type liver. PGC-1alpha seems to be dispensable for the rhythmic expression of this enzyme. Nevertheless, the mRNA levels of PEPCK are constitutively elevated at CT1 and CT13, in a similar way to the previous studies. Pyruvate dehydrogenase kinase 4 (PDK4) is a key regulator of the pyruvate dehydrogenase complex that controls the flux of pyruvate into the tricarboxylic acid cycle. The diurnal PDK4 expression is severely impaired in PGC-1alpha-deficient liver and skeletal muscle, although the phase of PDK4 oscillation seems to be preserved. Similarly, the cyclic expression of fatty acid binding protein 3 (Fabp3/H-FABP) as well as other mitochondrial genes involved in oxidative phosphorylation (OXPHOS), such as aconitase (Aco2) and Cox4a (Cox4i1), is also disrupted in PGC-1alpha null skeletal muscle. Together, the results illustrate that PGC-1alpha is essential for oscillatory expression of clock and metabolic genes in vivo.
Formal Description
Interaction-ID: 45373

affects_activity of

via PPARGC1A, ACO2, and COX4I1