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PDBsum entry 4c5h
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Transcription
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PDB id
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4c5h
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DOI no:
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Genes Dev
27:2367-2379
(2013)
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PubMed id:
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Structural basis for targeting the chromatin repressor Sfmbt to Polycomb response elements.
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C.Alfieri,
M.C.Gambetta,
R.Matos,
S.Glatt,
P.Sehr,
S.Fraterman,
M.Wilm,
J.Müller,
C.W.Müller.
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ABSTRACT
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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.
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');
}
}
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