Core promoter factor TAF9B regulates neuronal gene expression

Elife. 2014 Jul 8:3:e02559. doi: 10.7554/eLife.02559.

Abstract

Emerging evidence points to an unexpected diversification of core promoter recognition complexes that serve as important regulators of cell-type specific gene transcription. Here, we report that the orphan TBP-associated factor TAF9B is selectively up-regulated upon in vitro motor neuron differentiation, and is required for the transcriptional induction of specific neuronal genes, while dispensable for global gene expression in murine ES cells. TAF9B binds to both promoters and distal enhancers of neuronal genes, partially co-localizing at binding sites of OLIG2, a key activator of motor neuron differentiation. Surprisingly, in this neuronal context TAF9B becomes preferentially associated with PCAF rather than the canonical TFIID complex. Analysis of dissected spinal column from Taf9b KO mice confirmed that TAF9B also regulates neuronal gene transcription in vivo. Our findings suggest that alternative core promoter complexes may provide a key mechanism to lock in and maintain specific transcriptional programs in terminally differentiated cell types.DOI: http://dx.doi.org/10.7554/eLife.02559.001.

Keywords: TBP-associated factor TAF; motor neurons; neuronal enhancers; neuronal gene expression; stem cells; transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Embryonic Stem Cells / metabolism
  • Gene Expression Regulation, Developmental*
  • Mice, Knockout
  • Motor Neurons / cytology
  • Motor Neurons / metabolism*
  • Multiprotein Complexes / metabolism
  • Promoter Regions, Genetic*
  • Protein Binding
  • TATA-Binding Protein Associated Factors / genetics
  • TATA-Binding Protein Associated Factors / metabolism*
  • Transcription Factor TFIID / genetics
  • Transcription Factor TFIID / metabolism*
  • p300-CBP Transcription Factors / metabolism

Substances

  • Multiprotein Complexes
  • TAF9b protein, mouse
  • TATA-Binding Protein Associated Factors
  • Transcription Factor TFIID
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor