Molecular basis of PRC1 targeting to Polycomb response elements by PhoRC
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Molecular basis of PRC1 targeting to Polycomb response elements by PhoRC. / Frey, Felice; Sheahan, Thomas; Finkl, Katja; Stoehr, Gabriele; Mann, Matthias; Benda, Christian; Müller, Jürg.
In: Genes & Development, Vol. 30, No. 9, 01.05.2016, p. 1116-27.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Molecular basis of PRC1 targeting to Polycomb response elements by PhoRC
AU - Frey, Felice
AU - Sheahan, Thomas
AU - Finkl, Katja
AU - Stoehr, Gabriele
AU - Mann, Matthias
AU - Benda, Christian
AU - Müller, Jürg
N1 - © 2016 Frey et al.; Published by Cold Spring Harbor Laboratory Press.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Polycomb group (PcG) protein complexes repress transcription by modifying target gene chromatin. In Drosophila, this repression requires association of PcG protein complexes with cis-regulatory Polycomb response elements (PREs), but the interactions permitting formation of these assemblies are poorly understood. We show that the Sfmbt subunit of the DNA-binding Pho-repressive complex (PhoRC) and the Scm subunit of the canonical Polycomb-repressive complex 1 (PRC1) directly bind each other through their SAM domains. The 1.9 Å crystal structure of the Scm-SAM:Sfmbt-SAM complex reveals the recognition mechanism and shows that Sfmbt-SAM lacks the polymerization capacity of the SAM domains of Scm and its PRC1 partner subunit, Ph. Functional analyses in Drosophila demonstrate that Sfmbt-SAM and Scm-SAM are essential for repression and that PhoRC DNA binding is critical to initiate PRC1 association with PREs. Together, this suggests that PRE-tethered Sfmbt-SAM nucleates PRC1 recruitment and that Scm-SAM/Ph-SAM-mediated polymerization then results in the formation of PRC1-compacted chromatin.
AB - Polycomb group (PcG) protein complexes repress transcription by modifying target gene chromatin. In Drosophila, this repression requires association of PcG protein complexes with cis-regulatory Polycomb response elements (PREs), but the interactions permitting formation of these assemblies are poorly understood. We show that the Sfmbt subunit of the DNA-binding Pho-repressive complex (PhoRC) and the Scm subunit of the canonical Polycomb-repressive complex 1 (PRC1) directly bind each other through their SAM domains. The 1.9 Å crystal structure of the Scm-SAM:Sfmbt-SAM complex reveals the recognition mechanism and shows that Sfmbt-SAM lacks the polymerization capacity of the SAM domains of Scm and its PRC1 partner subunit, Ph. Functional analyses in Drosophila demonstrate that Sfmbt-SAM and Scm-SAM are essential for repression and that PhoRC DNA binding is critical to initiate PRC1 association with PREs. Together, this suggests that PRE-tethered Sfmbt-SAM nucleates PRC1 recruitment and that Scm-SAM/Ph-SAM-mediated polymerization then results in the formation of PRC1-compacted chromatin.
KW - Animals
KW - Chromatin
KW - Crystallography
KW - Drosophila Proteins
KW - Drosophila melanogaster
KW - Gene Expression Regulation
KW - Models, Molecular
KW - Polycomb Repressive Complex 1
KW - Polycomb-Group Proteins
KW - Polymerization
KW - Protein Binding
KW - Protein Structure, Tertiary
KW - Response Elements
KW - Journal Article
U2 - 10.1101/gad.279141.116
DO - 10.1101/gad.279141.116
M3 - Journal article
C2 - 27151979
VL - 30
SP - 1116
EP - 1127
JO - Genes & Development
JF - Genes & Development
SN - 0890-9369
IS - 9
ER -
ID: 186876710