H3K4me3 demethylation by the histone demethylase KDM5C/JARID1C promotes DNA replication origin firing

Beatrice Rondinelli, Hélène Schwerer, Elena Antonini, Marco Gaviraghi, Alessio Lupi, Michela Frenquelli, Davide Cittaro, Simona Segalla, Jean Marc Lemaitre, Giovanni Tonon

Research output: Contribution to journalArticlepeer-review

Abstract

DNA replication is a tightly regulated process that initiates from multiple replication origins and leads to the faithful transmission of the genetic material. For proper DNA replication, the chromatin surrounding origins needs to be remodeled. However, remarkably little is known on which epigenetic changes are required to allow the firing of replication origins. Here, we show that the histone demethylase KDM5C/JARID1C is required for proper DNA replication at early origins. JARID1C dictates the assembly of the pre-initiation complex, driving the binding to chromatin of the pre-initiation proteins CDC45 and PCNA, through the demethylation of the histone mark H3K4me3. Fork activation and histone H4 acetyla-tion, additional early events involved in DNA replication, are not affected by JARID1C downregulation. All together, these data point to a prominent role for JARID1C in a specific phase of DNA replication in mammalian cells, through its demethylase activity on H3K4me3.

Original languageEnglish
Pages (from-to)2560-2574
Number of pages15
JournalNucleic Acids Research
Volume43
Issue number5
DOIs
Publication statusPublished - Mar 11 2015

ASJC Scopus subject areas

  • Genetics

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