Dual functions of TAF7L in adipocyte differentiation

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-s...

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Main Authors: Haiying Zhou, Tommy Kaplan, Yan Li, Ivan Grubisic, Zhengjian Zhang, P Jeremy Wang, Michael B Eisen, Robert Tjian
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2013-01-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/00170
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author Haiying Zhou
Tommy Kaplan
Yan Li
Ivan Grubisic
Zhengjian Zhang
P Jeremy Wang
Michael B Eisen
Robert Tjian
author_facet Haiying Zhou
Tommy Kaplan
Yan Li
Ivan Grubisic
Zhengjian Zhang
P Jeremy Wang
Michael B Eisen
Robert Tjian
author_sort Haiying Zhou
collection DOAJ
description 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. 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 PPARγ at enhancers and TBP/Pol II at core promoters. In vitro binding studies confirmed that TAF7L forms complexes with both TBP and PPARγ. These findings suggest that TAF7L plays an integral role in adipocyte gene expression by targeting enhancers as a cofactor for PPARγ and promoters as a component of the core transcriptional machinery.
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spelling doaj.art-a6e7699797ab4c27ae5cdee1ed0000ec2022-12-22T03:52:17ZengeLife Sciences Publications LtdeLife2050-084X2013-01-01210.7554/eLife.00170Dual functions of TAF7L in adipocyte differentiationHaiying Zhou0Tommy Kaplan1Yan Li2Ivan Grubisic3Zhengjian Zhang4P Jeremy Wang5Michael B Eisen6Robert Tjian7Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States; Li Ka Shing Center For Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, California Institute of Quantitative Biosciences, University of California, Berkeley, United States; School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, IsraelJanelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesLi Ka Shing Center For Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, Berkeley, United States; UC Berkeley-UCSF Graduate Program in Bioengineering, Department of Molecular and Cell Biology, California Institute of Quantitative Biosciences, University of California, Berkeley, Berkeley, United StatesJanelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesDepartment of Animal Biology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, United StatesDepartment of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States; Department of Molecular and Cell Biology, California Institute of Quantitative Biosciences, University of California, Berkeley, United StatesDepartment of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States; Li Ka Shing Center For Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, Berkeley, United StatesThe 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. 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 PPARγ at enhancers and TBP/Pol II at core promoters. In vitro binding studies confirmed that TAF7L forms complexes with both TBP and PPARγ. These findings suggest that TAF7L plays an integral role in adipocyte gene expression by targeting enhancers as a cofactor for PPARγ and promoters as a component of the core transcriptional machinery.https://elifesciences.org/articles/00170ChIP-seqRNA-seqadipogenesisC3H10T½TAF7Ldifferentiation
spellingShingle Haiying Zhou
Tommy Kaplan
Yan Li
Ivan Grubisic
Zhengjian Zhang
P Jeremy Wang
Michael B Eisen
Robert Tjian
Dual functions of TAF7L in adipocyte differentiation
eLife
ChIP-seq
RNA-seq
adipogenesis
C3H10T½
TAF7L
differentiation
title Dual functions of TAF7L in adipocyte differentiation
title_full Dual functions of TAF7L in adipocyte differentiation
title_fullStr Dual functions of TAF7L in adipocyte differentiation
title_full_unstemmed Dual functions of TAF7L in adipocyte differentiation
title_short Dual functions of TAF7L in adipocyte differentiation
title_sort dual functions of taf7l in adipocyte differentiation
topic ChIP-seq
RNA-seq
adipogenesis
C3H10T½
TAF7L
differentiation
url https://elifesciences.org/articles/00170
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AT tommykaplan dualfunctionsoftaf7linadipocytedifferentiation
AT yanli dualfunctionsoftaf7linadipocytedifferentiation
AT ivangrubisic dualfunctionsoftaf7linadipocytedifferentiation
AT zhengjianzhang dualfunctionsoftaf7linadipocytedifferentiation
AT pjeremywang dualfunctionsoftaf7linadipocytedifferentiation
AT michaelbeisen dualfunctionsoftaf7linadipocytedifferentiation
AT roberttjian dualfunctionsoftaf7linadipocytedifferentiation