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Structures of human PRC2 with its cofactors AEBP2 and JARID2

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Science  23 Feb 2018:
Vol. 359, Issue 6378, pp. 940-944
DOI: 10.1126/science.aar5700

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Complete architecture of PRC2

Polycomb repressive complex 2 (PRC2) methylates lysine 27 in histone H3 to achieve gene silencing. Kasinath et al. report multiple structures of complete human PRC2 with its four core subunits (EZH2, EED, SUZ12, and RBAP48) and two cofactors (AEBP2 and JARID2) in different active states. These structures describe the molecular mimicry of H3 tails by AEBP2 and JARID2 to regulate PRC2 activity and reveal the organizational role of SUZ12 in maintaining the integrity and stability of the complex.

Science, this issue p. 940

Abstract

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 RBAP48 subunit, mimicking an unmodified H3 tail. SUZ12 interacts with all other subunits within the assembly and thus contributes to the stability of the complex. Our analysis defines the complete architecture of a functionally relevant PRC2 and provides a structural framework to understand its regulation by cofactors, histone tails, and RNA.

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