A Polycomb group protein complex with sequence-specific DNA-binding and selective methyl-lysine-binding activities
- Tetyana Klymenko1,
- Bernadett Papp1,
- Wolfgang Fischle2,3,
- Thomas Köcher1,
- Malgorzata Schelder1,
- Cornelia Fritsch1,
- Brigitte Wild1,
- Matthias Wilm1, and
- Jürg Müller1,4
- 1 Gene Expression Programme, European Molecular Biology Laboratory, 69117 Heidelberg, Germany;
- 2 Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10021, USA
- 3
↵3 Present address: Max Planck for Biophysical Chemistry, Laboratory of Chromatin Biochemistry, Am Fassberg 11, 37077 Goettingen, Germany.
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.
Keywords
Footnotes
- 4
↵4 Corresponding author.
↵4 E-MAIL Juerg.Mueller{at}embl.de; FAX 49-6221-387518.
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Supplemental material is available at http://www.genesdev.org.
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Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.377406
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- Received December 22, 2005.
- Accepted February 23, 2006.
- Copyright © 2006, Cold Spring Harbor Laboratory Press