Meis Cofactors Control HDAC and CBP Accessibility at Hox-Regulated Promoters during Zebrafish Embryogenesis

Seong Kyu Choe, Peiyuan Lu, Mako Nakamura, Jinhyup Lee, Charles G. Sagerström

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Hox proteins form complexes with Pbx and Meis cofactors to control gene expression, but the role of Meis is unclear. We demonstrate that Hoxb1-regulated promoters are highly acetylated on histone H4 (AcH4) and occupied by Hoxb1, Pbx, and Meis in zebrafish tissues where these promoters are active. Inhibition of Meis blocks gene expression and reduces AcH4 levels at these promoters, suggesting a role for Meis in maintaining AcH4. Within Hox transcription complexes, Meis binds directly to Pbx and we find that this binding displaces histone deacetylases (HDACs) from Hoxb1-regulated promoters in zebrafish embryos. Accordingly, Pbx mutants that cannot bind Meis act as repressors by recruiting HDACs and reducing AcH4 levels, while Pbx mutants that bind neither HDAC nor Meis are constitutively active and recruit CBP to increase AcH4 levels. We conclude that Meis acts, at least in part, by controlling access of HDAC and CBP to Hox-regulated promoters.

Original languageEnglish (US)
Pages (from-to)561-567
Number of pages7
JournalDevelopmental Cell
Volume17
Issue number4
DOIs
StatePublished - Oct 20 2009

Keywords

  • DEVBIO

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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