Universität zu Köln

Kasinath, Vignesh ORCID: 0000-0003-2686-0546, Beck, Curtis ORCID: 0000-0002-6674-9802, Sauer, Paul, Poepsel, Simon ORCID: 0000-0002-8304-4062, Kosmatka, Jennifer ORCID: 0000-0001-5337-3298, Faini, Marco ORCID: 0000-0001-8131-7648, Toso, Daniel, Aebersold, Ruedi ORCID: 0000-0002-9576-3267 and Nogales, Eva (2021). JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications. Science, 371 (6527). S. 362 - 397. WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1095-9203

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Abstract

Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) cooperate to determine cell identity by epigenetic gene expression regulation. However, the mechanism of PRC2 recruitment by means of recognition of PRC1-mediated H2AK119ub1 remains poorly understood. Our PRC2 cryo-electron microscopy structure with cofactors JARID2 and AEBP2 bound to a H2AK119ub1-containing nucleosome reveals a bridge helix in EZH2 that connects the SET domain, H3 tail, and nucleosomal DNA. JARID2 and AEBP2 each interact with one ubiquitin and the H2A-H2B surface. JARID2 stimulates PRC2 through interactions with both the polycomb protein EED and the H2AK119-ubiquitin, whereas AEBP2 has an additional scaffolding role. The presence of these cofactors partially overcomes the inhibitory effect that H3K4me3 and H3K36me3 exert on core PRC2 (in the absence of cofactors). Our results support a key role for JARID2 and AEBP2 in the cross-talk between histone modifications and PRC2 activity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kasinath, Vignesh UNSPECIFIED orcid.org/0000-0003-2686-0546 UNSPECIFIED Beck, Curtis UNSPECIFIED orcid.org/0000-0002-6674-9802 UNSPECIFIED Sauer, Paul UNSPECIFIED UNSPECIFIED UNSPECIFIED Poepsel, Simon UNSPECIFIED orcid.org/0000-0002-8304-4062 UNSPECIFIED Kosmatka, Jennifer UNSPECIFIED orcid.org/0000-0001-5337-3298 UNSPECIFIED Faini, Marco UNSPECIFIED orcid.org/0000-0001-8131-7648 UNSPECIFIED Toso, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Aebersold, Ruedi UNSPECIFIED orcid.org/0000-0002-9576-3267 UNSPECIFIED Nogales, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-594603
DOI:	10.1126/science.abc3393
Journal or Publication Title:	Science
Volume:	371
Number:	6527
Page Range:	S. 362 - 397
Date:	2021
Publisher:	AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication:	WASHINGTON
ISSN:	1095-9203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language STRUCTURAL BASIS; POLYCOMB; CHROMATIN; RECRUITMENT; COMPLEX; METHYLATION; INHIBITION; EFFICIENT; PROTEIN; ROBUST Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59460