Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Dual Functions of TAF7L in Adipocyte Differentiation

ABSTRACT: The diverse transcriptional mechanisms governing cellular differentiation and development of mammalian tissue remains poorly understood. Here we report that TAF7L, a paralogue of TFIID subunit TAF7, is enriched in adipocytes and mouse white fat tissue (WAT). Depletion of TAF7L reduced adipocyte-specific gene expression and compromised adipocyte differentiation as well as WAT development. Ectopic expression of TAF7L in myoblasts reprograms these muscle precursors into adipocytes upon induction. Genome-wide mRNA-seq expression profiling and ChIP-seq binding studies confirmed that TAF7L is required for activating adipocyte-specific genes via a dual mechanism wherein it interacts with PPARM-NM-3 at enhancers and TBP/Pol II at core promoters. In vitro binding studies confirmed that TAF7L forms complexes with both TBP and PPARM-NM-3. These findings suggest that TAF7L plays an integral role in adipocyte gene expression by targeting enhancers as a cofactor for PPARM-NM-3 and promoters as a component of the core transcriptional machinery. Genome-wide mapping of TAF7L and additional factors, and mRNA-seq expression profiling prior to and following mouse adipocyte differentiation.

ORGANISM(S): Mus musculus

SUBMITTER: Tommy Kaplan

PROVIDER: E-GEOD-41937 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Dual functions of TAF7L in adipocyte differentiation.

Zhou Haiying H Kaplan Tommy T Li Yan Y Grubisic Ivan I Zhang Zhengjian Z Wang P Jeremy PJ Eisen Michael B MB Tjian Robert R

eLife 20130108

The diverse transcriptional mechanisms governing cellular differentiation and development of mammalian tissue remains poorly understood. Here we report that TAF7L, a paralogue of TFIID subunit TAF7, is enriched in adipocytes and white fat tissue (WAT) in mouse. Depletion of TAF7L reduced adipocyte-specific gene expression, compromised adipocyte differentiation, and WAT development as well. Ectopic expression of TAF7L in myoblasts reprograms these muscle precursors into adipocytes upon induction. ...[more]

PMID: 23326641

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Project description:Histone variants complement and integrate histone post-translational modifications in regulating transcription. The histone variant macroH2A1 (mH2A1) is almost three times the size of its canonical H2A counterpart due to the presence of a ~25kDa evolutionarily conserved non-histone macro domain. Strikingly, mH2A1 can mediate both gene repression and activation. However, the molecular determinants conferring these alternative functions remain elusive. Here, we report that mH2A1.2 is required for the activation of the myogenic gene regulatory network and muscle cell differentiation. H3K27 acetylation at prospective enhancers is exquisitely sensitive to mH2A1.2, indicating a role of mH2A1.2 in imparting enhancer activation. Both H3K27 acetylation and recruitment of the transcription factor Pbx1 at prospective enhancers are regulated by mH2A1.2. Overall, our findings indicate a role of mH2A1.2 in marking regulatory regions for activation. To establish the role of the histone variant mH2A1.2 in skeletal muscle differentiation we employed the mouse skeletal muscle C2C12 cell line and examined the genome wide distribution mH2A1.2 in myoblast (MB) and myotube (MT) (two replicates). We intersected the distribution of mH2A1.2 with active (H3K4me3 and H3K4me1 from published dataset, and H3K27ac, two replicates) and repressive (H3K27me3, two replicates) epigenetic marks in MB and MT. To gain insite on how chromatin accessibility is remodelled when muscle cells are induced to differentiate, we performed ATAC-seq in C2C12 MB and MT (2 replicates). We then evaluated whether mH2A1.2 was involved in conferring H3K27 acetylation during skeletal muscle differentiation by performing H3K27ac ChIP-seq (two replicates) upon mH2A1.2i in MB and MT. We also prefomred the ChIP-Seq for transcription factor Pbx1 in control and mH2A1.2i cells in MT to address the potential role of mH2A in recruitment of Pbx1. RNA-seq experiments were performed in control and mH2A1.2i C2C12 cells at the stage of MB and MT (three replicates). When mH2A1.2i C2C12 MB were induced to differentiate, a global effect on transcription was observed.

Dataset Information

Dual Functions of TAF7L in Adipocyte Differentiation

Publications

Dual functions of TAF7L in adipocyte differentiation.

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