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

Fingerprint

RNA Interference
Heterochromatin
DNA Replication
Epigenomics
Methylation
Histones
DNA-Directed DNA Polymerase
Chromatin
Cell Cycle
Histone Code
Schizosaccharomyces
S Phase
Small Interfering RNA
RNA
Gene Expression

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

DNA replication, RNAi and epigenetic inheritance. / Gonzalez, Marlyn; Li, Fei.

In: Epigenetics, Vol. 7, No. 1, 01.2012, p. 14-19.

Research output: Contribution to journalArticle

Gonzalez, Marlyn ; Li, Fei. / DNA replication, RNAi and epigenetic inheritance. In: Epigenetics. 2012 ; Vol. 7, No. 1. pp. 14-19.
@article{0dc3a0937775454e8b3c480ef8b2c2c3,
title = "DNA replication, RNAi and epigenetic inheritance",
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.",
keywords = "Cell cycle, DNA replication, Epigenetic inheritance, Heterochromatin, Histone methylation, RNAi, Transcription",
author = "Marlyn Gonzalez and Fei Li",
year = "2012",
month = "1",
doi = "10.4161/epi.7.1.18545",
language = "English (US)",
volume = "7",
pages = "14--19",
journal = "Epigenetics",
issn = "1559-2294",
publisher = "Landes Bioscience",
number = "1",

}

TY - JOUR

T1 - DNA replication, RNAi and epigenetic inheritance

AU - Gonzalez, Marlyn

AU - Li, Fei

PY - 2012/1

Y1 - 2012/1

N2 - 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.

AB - 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.

KW - Cell cycle

KW - DNA replication

KW - Epigenetic inheritance

KW - Heterochromatin

KW - Histone methylation

KW - RNAi

KW - Transcription

UR - http://www.scopus.com/inward/record.url?scp=84856271742&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856271742&partnerID=8YFLogxK

U2 - 10.4161/epi.7.1.18545

DO - 10.4161/epi.7.1.18545

M3 - Article

VL - 7

SP - 14

EP - 19

JO - Epigenetics

JF - Epigenetics

SN - 1559-2294

IS - 1

ER -