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Cryo-EM structure of the full human PRC2 and regulation by AEBP2 and JARID2

ABSTRACT: Structural study of the PRC2 complex and its regulators AEPB2 and JARID2 combining cryo-EM, cross-linking, targeted MS and hydrogen/deuterium exchange MS.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Marco Faini

LAB HEAD: Ruedi Aebersold

PROVIDER: PXD008605 | Pride | 2018-01-25

REPOSITORIES: Pride

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			Action	DRS
	PRC2_A2J2_all_sequences.fasta	Fasta
	Results_summary.xlsx	Xlsx
	mfaini_D1607_170.raw	Raw
	mfaini_D1607_171.raw	Raw
	mfaini_D1607_173.raw	Raw

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Publications

Structures of human PRC2 with its cofactors AEBP2 and JARID2.

Kasinath Vignesh V Faini Marco M Poepsel Simon S Reif Dvir D Feng Xinyu Ashlee XA Stjepanovic Goran G Aebersold Ruedi R Nogales Eva E

Science (New York, N.Y.) 20180118 6378

Transcriptionally repressive histone H3 lysine 27 methylation by Polycomb repressive complex 2 (PRC2) is essential for cellular differentiation and development. Here we report cryo-electron microscopy structures of human PRC2 in a basal state and two distinct active states while in complex with its cofactors JARID2 and AEBP2. Both cofactors mimic the binding of histone H3 tails. JARID2, methylated by PRC2, mimics a methylated H3 tail to stimulate PRC2 activity, whereas AEBP2 interacts with the R ...[more]

PMID: 29348366

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Project description:The Polycomb Group proteins foster gene repression profiles required for proper development and unimpaired adulthood, and comprise the components of the PRC2 complex including the histone H3 lysine 27 (H3K27) methyltransferase Ezh2. How mammalian PRC2 accesses chromatin is unclear. We find that Jarid2 associates with PRC2 and stimulates its enzymatic activity in vitro. Jarid2 contains a Jumonji C domain, but is devoid of detectable histone demethylase activity. Instead, its artificial recruitment to a promoter in vivo resulted in co-recruitment of PRC2 with resultant increased levels of H3K27me2/3. Jarid2 co-localizes with Ezh2 and MTF2, a homologue of Drosophila Pcl, at endogenous genes in ES cells. Jarid2 can itself bind DNA and its recruitment in ES cells is interdependent with that of PRC2 as Jarid2 knockdown reduced PRC2 at its target promoters, and ES cells devoid of the PRC2 component EED are deficient in Jarid2 promoter access. In addition to the well-documented defects in embryonic viability upon down-regulation of Jarid2, ES cell differentiation is impaired, as is Oct4 silencing. Examination of two factors in ES cells

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