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Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains

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Fischle, Wolfgang, Wang, Yanming, Jacobs, Steven A., Kim, Youngchang, Allis, C. David, Khorasanizadeh, Sepideh·2003·Genes & Development

Abstract

On the histone H3 tail, Lys 9 and Lys 27 are both methylation sites associated with epigenetic repression, and reside within a highly related sequence motif ARKS. Here we show that the chromodomain proteins Polycomb (Pc) and HP1 ( h eterochromatin p rotein 1 ) are highly discriminatory for binding to these sites in vivo and in vitro. In Drosophila S2 cells, and on polytene chromosomes, methyl-Lys 27 and Pc are both excluded from areas that are enriched in methyl-Lys 9 and HP1. Swapping of the chromodomain regions of Pc and HP1 is sufficient for switching the nuclear localization patterns of these factors, indicating a role for their chromodomains in both target site binding and discrimination. To better understand the molecular basis for the selection of methyl-lysine binding sites, we solved the 1.8 Å structure of the Pc chromodomain in complex with a H3 peptide bearing trimethyl-Lys 27, and compared it with our previously determined structure of the HP1 chromodomain in complex with a H3 peptide bearing trimethyl-Lys 9. The Pc chromodomain distinguishes its methylation target on the H3 tail via an extended recognition groove that binds five additional residues preceding the ARKS motif.

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Metadata

Authors
Fischle, W., Wang, Y., Jacobs, S. A., Kim, Y., Allis, C. D., & Khorasanizadeh, S.
Venue
Genes & Development
Published
2003-08-01
Volume
17
Issue
15
Pages
1870-1881
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2118240383
Cited by
991
References
48
Type
posted content
Language
en
Open access
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Fischle, W., Wang, Y., Jacobs, S. A., Kim, Y., Allis, C. D., & Khorasanizadeh, S. (2003). Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes & Development. https://doi.org/10.1101/gad.1110503

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