Unique Structural Platforms of Suz12 Dictate Distinct Classes of PRC2 for Chromatin Binding

Siming Chen, Lianying Jiao, Murtada Shubbar, Xin Yang, Xin Liu

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Developmentally regulated accessory subunits dictate PRC2 function. Here, we report the crystal structures of a 120 kDa heterotetrameric complex consisting of Suz12, Rbbp4, Jarid2, and Aebp2 fragments that is minimally active in nucleosome binding and of an inactive binary complex of Suz12 and Rbbp4. Suz12 contains two unique structural platforms that define distinct classes of PRC2 holo complexes for chromatin binding. Aebp2 and Phf19 compete for binding of a non-canonical C2 domain of Suz12; Jarid2 and EPOP occupy an overlapped Suz12 surface required for chromatin association of PRC2. Suz12 and Aebp2 progressively block histone H3K4 binding to Rbbp4, suggesting that Rbbp4 may not be directly involved in PRC2 inhibition by the active H3K4me3 histone mark. Nucleosome binding enabled by Jarid2 and Aebp2 is in part accounted for by the structures, which also reveal that disruption of the Jarid2-Suz12 interaction may underlie the disease mechanism of an oncogenic chromosomal translocation of Suz12. Chen et al. solved the crystal structure of Suz12-Rbbp4-Jarid2-Aebp2 that provides important insights into PRC2 function and regulation, including the organization of PRC2 holo complexes, the binding of nucleosomes and histone tails, and a molecular consequence of an oncogenic chromosomal translocation of Suz12.

Original languageEnglish (US)
Pages (from-to)802-819.e1
JournalMolecular Cell
Volume69
Issue number5
DOIs
StatePublished - Mar 1 2018

Fingerprint

Nucleosomes
Chromatin
Genetic Translocation
Histones
Histone Code

Keywords

  • Aebp2
  • chromatin complex
  • development
  • gene silencing
  • H3K27me3
  • histone methylation
  • Jarid2
  • Polycomb repressive complex 2
  • PRC2
  • Rbbp4
  • Suz12

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Unique Structural Platforms of Suz12 Dictate Distinct Classes of PRC2 for Chromatin Binding. / Chen, Siming; Jiao, Lianying; Shubbar, Murtada; Yang, Xin; Liu, Xin.

In: Molecular Cell, Vol. 69, No. 5, 01.03.2018, p. 802-819.e1.

Research output: Contribution to journalArticle

Chen, Siming ; Jiao, Lianying ; Shubbar, Murtada ; Yang, Xin ; Liu, Xin. / Unique Structural Platforms of Suz12 Dictate Distinct Classes of PRC2 for Chromatin Binding. In: Molecular Cell. 2018 ; Vol. 69, No. 5. pp. 802-819.e1.
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