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

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...

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Bibliographic Details
Published in:Nucleic acids research 2015-03, Vol.43 (5), p.2560-2574
Main Authors: Rondinelli, Beatrice, Schwerer, Hélène, Antonini, Elena, Gaviraghi, Marco, Lupi, Alessio, Frenquelli, Michela, Cittaro, Davide, Segalla, Simona, Lemaitre, Jean-Marc, Tonon, Giovanni
Format: Article
Language:English
Subjects:
Cell Cycle
Cell Cycle Proteins - metabolism
Chromatin - genetics
Chromatin - metabolism
DNA Replication
Gene regulation, Chromatin and Epigenetics
HeLa Cells
Histone Demethylases
Histones - metabolism
Humans
Immunoblotting
Life Sciences
Lysine - metabolism
Methylation
Oxidoreductases, N-Demethylating - genetics
Oxidoreductases, N-Demethylating - metabolism
Proliferating Cell Nuclear Antigen - metabolism
Protein Binding
Replication Origin
RNA Interference
Time Factors
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Summary: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.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkv090