Non-canonical TAF complexes regulate active promoters in human embryonic stem cells
UMass Chan AffiliationsProgram in Molecular Medicine
Program in Gene Function and Expression
Document TypeJournal Article
KeywordsTATA-Box Binding Protein
TATA-Binding Protein Associated Factors
Transcription Factors, General
Embryonic Stem Cells
Genetics and Genomics
MetadataShow full item record
AbstractThe general transcription factor TFIID comprises the TATA-box-binding protein (TBP) and approximately 14 TBP-associated factors (TAFs). Here we find, unexpectedly, that undifferentiated human embryonic stem cells (hESCs) contain only six TAFs (TAFs 2, 3, 5, 6, 7 and 11), whereas following differentiation all TAFs are expressed. Directed and global chromatin immunoprecipitation analyses reveal an unprecedented promoter occupancy pattern: most active genes are bound by only TAFs 3 and 5 along with TBP, whereas the remaining active genes are bound by TBP and all six hESC TAFs. Consistent with these results, hESCs contain a previously undescribed complex comprising TAFs 2, 6, 7, 11 and TBP. Altering the composition of hESC TAFs, either by depleting TAFs that are present or ectopically expressing TAFs that are absent, results in misregulated expression of pluripotency genes and induction of differentiation. Thus, the selective expression and use of TAFs underlies the ability of hESCs to self-renew.
Maston et al. eLife 2012;1:e00068. DOI: 10.7554/eLife.00068. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/44004
Supplementary file is also available at http://dx.doi.org/10.7554/eLife.00068.026.
The following datasets were generated: Maston GA, Green MR, Zhu LJ, Chamberlain L, Lin L, 2012, ChIP-chip from H9 hESCs for RNA Polymerase II, TBP, TAF3, TAF5, TAF7, and TAF11, GSE39312; http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE39312, In the public domain at GEO: http://www.ncbi.nlm.nih.gov/geo/.
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