Coordinated regulation of heterochromatin inheritance by Dpb3–Dpb4 complex

Haijin He, Yang Li, Qianhua Dong, An Yun Chang, Feng Gao, Zhongxuan Chi, Min Su, Faben Zhang, Hyoju Ban, Rob Martienssen, Yu Hang Chen, Fei Li

Research output: Contribution to journalArticlepeer-review

Abstract

During DNA replication, chromatin is disrupted ahead of the replication fork, and epigenetic information must be restored behind the fork. How epigenetic marks are inherited through DNA replication remains poorly understood. Histone H3 lysine 9 (H3K9) methylation and histone hypoacetylation are conserved hallmarks of heterochromatin. We previously showed that the inheritance of H3K9 methylation during DNA replication depends on the catalytic subunit of DNA polymerase epsilon, Cdc20. Here we show that the histone-fold subunit of Pol epsilon, Dpb4, interacts an uncharacterized small histone-fold protein, SPCC16C4.22, to form a heterodimer in fission yeast. We demonstrate that SPCC16C4.22 is nonessential for viability and corresponds to the true ortholog of Dpb3. We further show that the Dpb3–Dpb4 dimer associates with histone deacetylases, chromatin remodelers, and histones and plays a crucial role in the inheritance of histone hypoacetylation in heterochromatin. We solve the 1.9-Å crystal structure of Dpb3–Dpb4 and reveal that they form the H2A–H2B-like dimer. Disruption of Dpb3–Dpb4 dimerization results in loss of heterochromatin silencing. Our findings reveal a link between histone deacetylation and H3K9 methylation and suggest a mechanism for how two processes are coordinated during replication. We propose that the Dpb3–Dpb4 heterodimer together with Cdc20 serves as a platform for the recruitment of chromatin modifiers and remodelers that mediate heterochromatin assembly during DNA replication, and ensure the faithful inheritance of epigenetic marks in heterochromatin.

Original languageEnglish (US)
Pages (from-to)12524-12529
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number47
DOIs
StatePublished - Nov 21 2017

Keywords

  • DNA polymerase epsilon
  • Epigenetic inheritance
  • Heterochromatin
  • Replication
  • Schizosaccharomyces pombe

ASJC Scopus subject areas

  • General

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