Structural basis for targeting the chromatin repressor Sfmbt to Polycomb response elements.

Détails

ID Serval
serval:BIB_90A093D277B3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Structural basis for targeting the chromatin repressor Sfmbt to Polycomb response elements.
Périodique
Genes & development
Auteur(s)
Alfieri C., Gambetta M.C., Matos R., Glatt S., Sehr P., Fraterman S., Wilm M., Müller J., Müller C.W.
ISSN
1549-5477 (Electronic)
ISSN-L
0890-9369
Statut éditorial
Publié
Date de publication
01/11/2013
Peer-reviewed
Oui
Volume
27
Numéro
21
Pages
2367-2379
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Polycomb group (PcG) protein complexes repress developmental regulator genes by modifying their chromatin. How different PcG proteins assemble into complexes and are recruited to their target genes is poorly understood. Here, we report the crystal structure of the core of the Drosophila PcG protein complex Pleiohomeotic (Pho)-repressive complex (PhoRC), which contains the Polycomb response element (PRE)-binding protein Pho and Sfmbt. The spacer region of Pho, separated from the DNA-binding domain by a long flexible linker, forms a tight complex with the four malignant brain tumor (4MBT) domain of Sfmbt. The highly conserved spacer region of the human Pho ortholog YY1 binds three of the four human 4MBT domain proteins in an analogous manner but with lower affinity. Comparison of the Drosophila Pho:Sfmbt and human YY1:MBTD1 complex structures provides a molecular explanation for the lower affinity of YY1 for human 4MBT domain proteins. Structure-guided mutations that disrupt the interaction between Pho and Sfmbt abolish formation of a ternary Sfmbt:Pho:DNA complex in vitro and repression of developmental regulator genes in Drosophila. PRE tethering of Sfmbt by Pho is therefore essential for Polycomb repression in Drosophila. Our results support a model where DNA tethering of Sfmbt by Pho and multivalent interactions of Sfmbt with histone modifications and other PcG proteins create a hub for PcG protein complex assembly at PREs.
Mots-clé
Amino Acid Sequence, Animals, Chromosomal Proteins, Non-Histone/chemistry, Chromosomal Proteins, Non-Histone/metabolism, Drosophila Proteins/chemistry, Drosophila Proteins/genetics, Drosophila Proteins/metabolism, Drosophila melanogaster/chemistry, Drosophila melanogaster/genetics, Drosophila melanogaster/metabolism, Gene Expression Regulation, Developmental, Humans, Models, Molecular, Molecular Sequence Data, Mutation/genetics, Polycomb-Group Proteins/chemistry, Polycomb-Group Proteins/genetics, Polycomb-Group Proteins/metabolism, Protein Binding, Protein Stability, Protein Structure, Quaternary, Protein Structure, Tertiary, Sequence Alignment, YY1 Transcription Factor/chemistry, YY1 Transcription Factor/metabolism, Pho, PhoRC, Polycomb, Polycomb response element, Sfmbt, YY1
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/07/2018 11:01
Dernière modification de la notice
21/08/2019 6:35
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