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

Autor: Matthias Wilm, Sebastian Glatt, Christoph W. Müller, Raquel Matos, Peter Sehr, Jürg Müller, Maria Cristina Gambetta, Sven Fraterman, Claudio Alfieri
Jazyk: angličtina
Rok vydání: 2013
Předmět:
inorganic chemicals
Models
Molecular
Histone methyltransferase activity
animal structures
genetic structures
Chromosomal Proteins
Non-Histone
Molecular Sequence Data
Repressor
Polycomb-Group Proteins
macromolecular substances
Trithorax-group proteins
03 medical and health sciences
0302 clinical medicine
Genetics
Polycomb-group proteins
Animals
Drosophila Proteins
Humans
Amino Acid Sequence
Protein Structure
Quaternary
YY1 Transcription Factor
030304 developmental biology
0303 health sciences
biology
urogenital system
Protein Stability
PcG protein complex
fungi
Gene Expression Regulation
Developmental
Chromatin
Cell biology
Protein Structure
Tertiary
Histone
Drosophila melanogaster
Mutation
biology.protein
Sequence Alignment
030217 neurology & neurosurgery
Drosophila Protein
Developmental Biology
Research Paper
Protein Binding
Zdroj: Genes & Development; Vol 27
ISSN: 0890-9369
DOI: 10.1101/gad.226621.113
Popis: 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.
Databáze: OpenAIRE
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