1. Developmental Biology
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TAF7L modulates brown adipose tissue formation

  1. Haiying Zhou
  2. Bo Wan
  3. Ivan Grubisic
  4. Tommy Kaplan
  5. Robert Tjian  Is a corresponding author
  1. Howard Hughes Medical Institute, University of California, Berkeley, United States
  2. Fudan University, China
  3. Li Ka Shing Center For Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, United States
  4. The Hebrew University of Jerusalem, Israel
Research Article
  • Cited 13
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Cite this article as: eLife 2014;3:e02811 doi: 10.7554/eLife.02811

Abstract

Brown adipose tissue (BAT) plays an essential role in metabolic homeostasis by dissipating energy via thermogenesis through uncoupling protein 1 (UCP1). Previously, we reported that the TATA-binding protein associated factor 7L (TAF7L) is an important regulator of white adipose tissue (WAT) differentiation. Here, we show that TAF7L also serves as a molecular switch between brown fat and muscle lineages in vivo and in vitro. In adipose tissue, TAF7L-containing TFIID complexes associate with PPARγ to mediate DNA looping between distal enhancers and core promoter elements. Our findings suggest that presence of the tissue-specific TAF7L subunit in TFIID functions to promote long-range chromatin interactions during BAT lineage specification.

Article and author information

Author details

  1. Haiying Zhou

    Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  2. Bo Wan

    Fudan University, Shanghai, China
    Competing interests
    No competing interests declared.
  3. Ivan Grubisic

    Li Ka Shing Center For Biomedical and Health Sciences, CIRM Center of Excellence, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
  4. Tommy Kaplan

    The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    No competing interests declared.
  5. Robert Tjian

    Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
    For correspondence
    tjianr@hhmi.org
    Competing interests
    Robert Tjian, Robert Tjian is President of the Howard Hughes Medical Institute (2009-present), one of the three founding funders of eLife..

Ethics

Animal experimentation: All animal experiments were performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to animal use protocols (#R007) approved by the Institutional Animal Care and Use Committee (IACUC) of the University of California, Berkeley.

Reviewing Editor

  1. James T Kadonaga, University of California, San Diego, United States

Publication history

  1. Received: March 16, 2014
  2. Accepted: May 25, 2014
  3. Accepted Manuscript published: May 29, 2014 (version 1)
  4. Version of Record published: June 24, 2014 (version 2)

Copyright

© 2014, Zhou et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

    1. Cell Biology
    2. Developmental Biology
    Haiying Zhou et al.
    Research Article

    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.

    1. Developmental Biology
    2. Chromosomes and Gene Expression
    Katherine A Jones
    Insight

    Different members of the TAF family of proteins work in differentiated cells, such as motor neurons or brown fat cells, to control the expression of genes that are specific to each cell type.