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

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...

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Autores principales: Wu, Rentian, Wang, Zhiquan, Zhang, Honglian, Gan, Haiyun, Zhang, Zhiguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5224507/
https://www.ncbi.nlm.nih.gov/pubmed/27679476
http://dx.doi.org/10.1093/nar/gkw848
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author Wu, Rentian
Wang, Zhiquan
Zhang, Honglian
Gan, Haiyun
Zhang, Zhiguo
author_facet Wu, Rentian
Wang, Zhiquan
Zhang, Honglian
Gan, Haiyun
Zhang, Zhiguo
author_sort Wu, Rentian
collection PubMed
description 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 pre-replicative 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 δ, 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.
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spelling pubmed-52245072017-01-17 H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication Wu, Rentian Wang, Zhiquan Zhang, Honglian Gan, Haiyun Zhang, Zhiguo Nucleic Acids Res Gene regulation, Chromatin and Epigenetics 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 pre-replicative 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 δ, 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. Oxford University Press 2017-01-09 2016-09-26 /pmc/articles/PMC5224507/ /pubmed/27679476 http://dx.doi.org/10.1093/nar/gkw848 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Wu, Rentian
Wang, Zhiquan
Zhang, Honglian
Gan, Haiyun
Zhang, Zhiguo
H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication
title H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication
title_full H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication
title_fullStr H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication
title_full_unstemmed H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication
title_short H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication
title_sort h3k9me3 demethylase kdm4d facilitates the formation of pre-initiative complex and regulates dna replication
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5224507/
https://www.ncbi.nlm.nih.gov/pubmed/27679476
http://dx.doi.org/10.1093/nar/gkw848
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