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

Beatrice Rondinelli | Zendy; Hélène Schwerer | Zendy; Elena Antonini | Zendy; Marco Gaviraghi | Zendy; Alessio Lupi | Zendy; Michela Frenquelli | Zendy; Davide Cittaro | Zendy; Simona Segalla | Zendy; Jean-Marc Lemaı̂tre | Zendy; Giovanni To | Zendy

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

Author(s) -

Beatrice Rondinelli,

Hélène Schwerer,

Elena Antonini,

Marco Gaviraghi,

Alessio Lupi,

Michela Frenquelli,

Davide Cittaro,

Simona Segalla,

Jean-Marc Lemaı̂tre,

Giovanni To

Publication year - 2015

Publication title -

nucleic acids research

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 9.008

H-Index - 537

eISSN - 1362-4954

pISSN - 0305-1048

DOI - 10.1093/nar/gkv090

Subject(s) - biology , demethylase , h3k4me3 , control of chromosome duplication , dna replication , histone code , histone , origin recognition complex , histone methylation , eukaryotic dna replication , chromatin , genetics , microbiology and biotechnology , dna methylation , dna , nucleosome , promoter , gene , gene expression

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 acetylation, 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.

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