Genomics

Dataset Information

156

An HDAC3-PROX1 Corepressor Module Acts on HNF4α to Control Hepatic Triglycerides


ABSTRACT: The histone deacetylase HDAC3 is a critical mediator of hepatic lipid metabolism, and liver-specific deletion of HDAC3 leads to fatty liver. To elucidate the underlying mechanism we developed a method of cross-linking followed by mass spectrometry to define a high-confidence HDAC3 interactome in vivo that includes the canonical NCoR/HDAC3 complex as well as Prospero-related homeobox 1 protein (PROX1). HDAC3 and PROX1 co-localize extensively on the mouse liver genome, and are co-recruited by Hepatocyte Nuclear Factor 4α (HNF4α). The HDAC3-PROX1 module controls the expression of a gene program regulating lipid homeostasis, and hepatic-specific ablation of either component increases triglyceride content in liver. These findings underscore the importance of specific combinations of transcription factors and coregulators in the fine tuning of organismal metabolism. Overall design: Biological replicates were uploaded in separated files and indicated in the file names.

INSTRUMENT(S): Illumina HiSeq 2000 (Mus musculus)

SUBMITTER: Manashree Damle  

PROVIDER: GSE90533 | GEO | 2017-07-26

SECONDARY ACCESSION(S): PRJNA354961

REPOSITORIES: GEO

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Publications

An HDAC3-PROX1 corepressor module acts on HNF4α to control hepatic triglycerides.

Armour Sean M SM   Remsberg Jarrett R JR   Damle Manashree M   Sidoli Simone S   Ho Wesley Y WY   Li Zhenghui Z   Garcia Benjamin A BA   Lazar Mitchell A MA  

Nature communications 20170915 1


The histone deacetylase HDAC3 is a critical mediator of hepatic lipid metabolism, and liver-specific deletion of HDAC3 leads to fatty liver. To elucidate the underlying mechanism, here we report a method of cross-linking followed by mass spectrometry to define a high-confidence HDAC3 interactome in vivo that includes the canonical NCoR-HDAC3 complex as well as Prospero-related homeobox 1 protein (PROX1). HDAC3 and PROX1 co-localize extensively on the mouse liver genome, and are co-recruited by h  ...[more]

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