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 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.DOI:http://dx.doi.org/10.7554/eLife.00170.001.
Keywords:
C3H10T½; ChIP-seq; Mouse; RNA-seq; TAF7L; adipogenesis; differentiation.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
3T3-L1 Cells
-
Adipocytes / metabolism*
-
Adipogenesis* / genetics
-
Adipose Tissue, White / cytology
-
Adipose Tissue, White / metabolism*
-
Animals
-
Binding Sites
-
Cellular Reprogramming
-
Chromatin Immunoprecipitation
-
Enhancer Elements, Genetic
-
Gene Expression Profiling
-
Gene Expression Regulation
-
HEK293 Cells
-
HeLa Cells
-
Humans
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Myoblasts / metabolism
-
PPAR gamma / metabolism
-
Promoter Regions, Genetic
-
RNA, Messenger / metabolism
-
Signal Transduction
-
TATA-Binding Protein Associated Factors / deficiency
-
TATA-Binding Protein Associated Factors / genetics
-
TATA-Binding Protein Associated Factors / metabolism*
-
TATA-Box Binding Protein / metabolism
-
Transcription Factor TFIID / deficiency
-
Transcription Factor TFIID / genetics
-
Transcription Factor TFIID / metabolism*
-
Transcription Factors / deficiency
-
Transcription Factors / genetics
-
Transcription Factors / metabolism*
-
Transcription, Genetic
-
Transfection
Substances
-
PPAR gamma
-
RNA, Messenger
-
TAF7L protein, mouse
-
TATA-Binding Protein Associated Factors
-
TATA-Box Binding Protein
-
Transcription Factor TFIID
-
Transcription Factors