H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication

Rentian Wu, Zhiquan Wang, Honglian Zhang, Haiyun Gan, Zhiguo Zhang

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

DNA replication is tightly regulated to occur once and only once per cell cycle. How chromatin, the physiological substrate of DNA replication machinery, regulates DNA replication remains largely unknown. Here we show that histone H3 lysine 9 demethylase Kdm4d regulates DNA replication in eukaryotic cells. Depletion of Kdm4d results in defects in DNA replication, which can be rescued by the expression of H3K9M, a histone H3 mutant transgene that reverses the effect of Kdm4d on H3K9 methylation. Kdm4d interacts with replication proteins, and its recruitment to DNA replication origins depends on the two prereplicative complex components (origin recognition complex [ORC] and minichromosome maintenance [MCM] complex). Depletion of Kdm4d impairs the recruitment of Cdc45, proliferating cell nuclear antigen (PCNA), and polymerase, but not ORC and MCM proteins. These results demonstrate a novel mechanism by which Kdm4d regulates DNA replication by reducing the H3K9me3 level to facilitate formation of pre-initiative complex.

Original languageEnglish (US)
Pages (from-to)169-180
Number of pages12
JournalNucleic Acids Research
Volume45
Issue number1
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

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DNA Replication
Origin Recognition Complex
Histones
Minichromosome Maintenance Proteins
Replication Origin
Proliferating Cell Nuclear Antigen
Eukaryotic Cells
Transgenes
Methylation
Lysine
Chromatin
Cell Cycle
Maintenance
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication. / Wu, Rentian; Wang, Zhiquan; Zhang, Honglian; Gan, Haiyun; Zhang, Zhiguo.

In: Nucleic Acids Research, Vol. 45, No. 1, 01.01.2017, p. 169-180.

Research output: Contribution to journalArticle

Wu, Rentian ; Wang, Zhiquan ; Zhang, Honglian ; Gan, Haiyun ; Zhang, Zhiguo. / H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication. In: Nucleic Acids Research. 2017 ; Vol. 45, No. 1. pp. 169-180.
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