KDM2B Recruitment of the Polycomb Group Complex, PRC1.1, Requires Cooperation between PCGF1 and BCORL1

Sarah J. Wong, Micah D. Gearhart, Alexander B. Taylor, David R. Nanyes, Daniel J. Ha, Angela K. Robinson, Jason A. Artigas, Oliver J. Lee, Borries Demeler, P. John Hart, Vivian J. Bardwell, Chongwoo A. Kim

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

KDM2B recruits H2A-ubiquitinating activity of a non-canonical Polycomb Repression Complex 1 (PRC1.1) to CpG islands, facilitating gene repression. We investigated the molecular basis of recruitment using in vitro assembly assays to identify minimal components, subcomplexes, and domains required for recruitment. A minimal four-component PRC1.1 complex can be assembled by combining two separately isolated subcomplexes: the DNA-binding KDM2B/SKP1 heterodimer and the heterodimer of BCORL1 and PCGF1, a core component of PRC1.1. The crystal structure of the KDM2B/SKP1/BCORL1/PCGF1 complex illustrates the crucial role played by the PCGF1/BCORL1 heterodimer. The BCORL1 PUFD domain positions residues preceding the RAWUL domain of PCGF1 to create an extended interface for interaction with KDM2B, which is unique to the PCGF1-containing PRC1.1 complex. The structure also suggests how KDM2B might simultaneously function in PRC1.1 and an SCF ubiquitin ligase complex and the possible molecular consequences of BCOR PUFD internal tandem duplications found in pediatric kidney and brain tumors.

Original languageEnglish (US)
Pages (from-to)1795-1801
Number of pages7
JournalStructure
Volume24
Issue number10
DOIs
StatePublished - Oct 4 2016

Bibliographical note

Funding Information:
C.A.K. was supported by the Welch Foundation ( AQ-1813 ) and the NIGMS of the NIH under award number R01GM114338 . S.J.W. was supported by the NIH ( F31GM099418 ). V.J.B. was supported by the NIH ( R01CA071540 ) and funds from the Minnesota Masonic Charities , and the University of Minnesota Medical School . B.D. acknowledges support from the National Science Foundation ( ACI-1339649 ) and XSEDE ( MCB-070039 ). P.J.H. was supported by the Welch Foundation ( AQ-1399 ). The University of Texas Health Science Center at San Antonio (UTHSCSA) X-ray Crystallography Core Laboratory is supported in part by the Vice President for Research and a National Cancer Institute P30 Cancer Center Support Grant ( CA054174 ) awarded to the CTRC at UTHSCSA. NECAT beamline 24-ID-C is supported in part by the NIH ( P41GM103403 ) and the DOE ( DE-AC02–06CH11357

Publisher Copyright:
© 2016 Elsevier Ltd

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