DNA replication, RNAi and epigenetic inheritance

Marlyn Gonzalez, Fei Li

Research output: Contribution to journalArticle

Abstract

Epigenetic marks, such as histone methylation, play a centralrole in chromatin structure and gene expression. DuringDNA replication, chromatin undergoes a wave of disruptionand reassembly. Little is known about how the epigenetic marks are faithfully inherited from one generation to the next. In fission yeast, the hallmark of heterochromatin, a condensed chromatin structure, is H3K9 methylation. This conserved epigenetic mark is mediated by small interference RNAs (siRNAs) in a cell cycle-dependent manner: at S phase, heterochromatin is briefly transcribed by RNAP II and the transcripts are subsequently processed into siRNAs. These small RNAs, together with other key silencing factors, including Dos1/Raf1/Clr8/Cmc1, Dos2/Raf2/Clr7/Cmc2 and Rik1, mediate H3K9 methylation by the histone H3K9 methyltransferase Clr4. Our recent findings indicate that the ε subunit of DNA polymerase, Cdc20, associates with the Dos2-Rik1 complex and is essential for H3K9 methylation and heterochromatin function. Moreover, Cdc20 regulates siRNA generation by promoting RNAP II transcription of heterochromatin. These data suggest that DNA polymerase components may play a key role in the inheritance of histone methylation by coordinating DNA replication, RNAi and histone methylation, and explain previously observed cell cycle-regulated RNAidependent heterochromatin silencing. We propose a model in which, at DNA replication forks, DNA polymerase subunits mediate the recruitment of epigenetic factors required for RNAi and histone modification to heterochromatin to promote the faithful transmission of histone methylation.

Original languageEnglish (US)
Pages (from-to)14-19
Number of pages6
JournalEpigenetics
Volume7
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • Cell cycle
  • DNA replication
  • Epigenetic inheritance
  • Heterochromatin
  • Histone methylation
  • RNAi
  • Transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'DNA replication, RNAi and epigenetic inheritance'. Together they form a unique fingerprint.

  • Cite this