A polycomb group protein complex with sequence-specific DNA-binding and selective methyl-lysine-binding activities

Tetyana Klymenko, Bernadett Papp, Wolfgang Fischle, Thomas Köcher, Malgorzata Schelder, Cornelia Fritsch, Brigitte Wild, Matthias Wilm, Jürg Müller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

282 Scopus citations

Abstract

Polycomb response elements (PREs) are specific cis-regulatory sequences needed for transcriptional repression of HOX and other target genes by Polycomb group (PcG) proteins. Among the many PcG proteins known in Drosophila, Pho is the only sequence-specific DNA-binding protein. To gain insight into the function of Pho, we purified Pho protein complexes from Drosophila embryos and found that Pho exists in two distinct protein assemblies: a Pho-dINO80 complex containing the Drosophila INO80 nucleosome-remodeling complex, and a Pho-repressive complex (PhoRC) containing the uncharacterized gene product dSfmbt. Analysis of PhoRC reveals that dSfmbt is a novel PcG protein that is essential for HOX gene repression in Drosophila. PhoRC is bound at HOX gene PREs in vivo, and this targeting strictly depends on Pho-binding sites. Characterization of dSfmbt protein shows that its MBT repeats have unique discriminatory binding activity for methylated lysine residues in histones H3 and H4; the MBT repeats bind mono- and di-methylated H3-K9 and H4-K20 but fail to interact with these residues if they are unmodified or tri-methylated. Our results establish PhoRC as a novel Drosophila PcG protein complex that combines DNA-targeting activity (Pho) with a unique modified histone-binding activity (dSfmbt). We propose that PRE-tethered PhoRC selectively interacts with methylated histones in the chromatin flanking PREs to maintain a Polycomb-repressed chromatin state.

Original languageEnglish (US)
Pages (from-to)1110-1122
Number of pages13
JournalGenes and Development
Volume20
Issue number9
DOIs
StatePublished - May 1 2006

Keywords

  • Histone methylation
  • MBT repeat
  • PRE
  • Pho/dYY1
  • Polycomb group

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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