Smads orchestrate specific histone modifications and chromatin remodeling to activate transcription

Sarah Ross, Edwin Cheung, Thodoris G. Petrakis, Michael Howell, W. Lee Kraus, Caroline S. Hill

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Smads are intracellular transducers for TGF-β superfamily ligands, but little is known about the mechanism by which complexes of receptor- phosphorylated Smad2 and Smad4 regulate transcription. Using an in vitro transcription system, we have discovered that, unlike most transcription factors that are sufficient to recruit the basal transcription machinery and therefore activate transcription on both naked DNA and chromatin templates, the Smads only activate transcription from chromatin templates. We demonstrate that Smad2-mediated transcription requires the histone acetyltransferase, p300. Smad2-recruited p300 exhibits an altered substrate specificity, specifically acetylating nucleosomal histone H3 at lysines 9 and 18, and these modifications are also detected on an endogenous Smad2-dependent promoter in a ligand-induced manner. Furthermore, we show that endogenous Smad2 interacts with the SWI/SNF ATPase, Brg1, in a TGF-β-dependent manner, and demonstrate that Brg1 is recruited to Smad2-dependent promoters and is specifically required for TGF-β-induced expression of endogenous Smad2 target genes. Our data indicate that the Smads define a new class of transcription factors that absolutely require chromatin to assemble the basal transcription machinery and activate transcription.

Original languageEnglish (US)
Pages (from-to)4490-4502
Number of pages13
JournalEMBO Journal
Volume25
Issue number19
DOIs
StatePublished - Oct 4 2006

Fingerprint

Histone Code
Chromatin Assembly and Disassembly
Transcription
Histones
Chromatin
Transcription Factors
Ligands
Histone Acetyltransferases
Substrate Specificity
Transducers
Lysine
Adenosine Triphosphatases
Machinery
DNA
Genes

Keywords

  • Brg1
  • Chromatin
  • Smad
  • TGF-β
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Smads orchestrate specific histone modifications and chromatin remodeling to activate transcription. / Ross, Sarah; Cheung, Edwin; Petrakis, Thodoris G.; Howell, Michael; Kraus, W. Lee; Hill, Caroline S.

In: EMBO Journal, Vol. 25, No. 19, 04.10.2006, p. 4490-4502.

Research output: Contribution to journalArticle

Ross, Sarah ; Cheung, Edwin ; Petrakis, Thodoris G. ; Howell, Michael ; Kraus, W. Lee ; Hill, Caroline S. / Smads orchestrate specific histone modifications and chromatin remodeling to activate transcription. In: EMBO Journal. 2006 ; Vol. 25, No. 19. pp. 4490-4502.
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