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 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.

• Publication year

  2015

• Venue

  Nucleic Acids Research

• Publication date

  2015-02-23

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1093/nar/gkv090PMID 25712104PMCID 4357704
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Replication and Active Demethylation Represent Partially Overlapping Mechanisms for Erasure of H3K4me3 in Budding Yeast

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• H3 K36 Methylation Helps Determine the Timing of Cdc45 Association with Replication Origins

  2009cited by this paper
• HBO1 histone acetylase is a coactivator of the replication licensing factor Cdt1.

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• DNA replication timing of the human beta-globin domain is controlled by histone modification at the origin.

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• An ARS element inhibits DNA replication through a SIR2-dependent mechanism.

  2008cited by this paper
• Direct Interaction between SET8 and Proliferating Cell Nuclear Antigen Couples H4-K20 Methylation with DNA Replication*

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  2007cited by this paper
• The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases.

  2007influential reference
• Cell cycle regulation of DNA replication.

  2007influential reference
• The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation

  2007cited by this paper
• Regulation of Replication Fork Progression Through Histone Supply and Demand

  2007cited by this paper
• Chromatin challenges during DNA replication and repair.

  2007cited by this paper
• PCNA, the maestro of the replication fork.

  2007cited by this paper
• PR-Set7–dependent lysine methylation ensures genome replication and stability through S phase

  2007cited by this paper
• Distinct roles for Sld3 and GINS during establishment and progression of eukaryotic DNA replication forks

  2006cited by this paper
• Structural insights into histone demethylation by JMJD2 family members.

  2006cited by this paper
• Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae

  2006influential reference
• Acute Reduction of an Origin Recognition Complex (ORC) Subunit in Human Cells Reveals a Requirement of ORC for Cdk2 Activation*

  2005cited by this paper
• Mutations in the JARID1C gene, which is involved in transcriptional regulation and chromatin remodeling, cause X-linked mental retardation.

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  2004cited by this paper
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  2004cited by this paper
• Dynamics of pre-replication complex proteins during the cell division cycle.

  2004cited by this paper
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  2003cited by this paper
• A novel ring-like complex of Xenopus proteins essential for the initiation of DNA replication.

  2003cited by this paper
• Inhibiting the expression of DNA replication-initiation proteins induces apoptosis in human cancer cells.

  2003cited by this paper
• DNA replication in eukaryotic cells.

  2002cited by this paper
• Cell type-specific responses of human cells to inhibition of replication licensing

  2002cited by this paper
• ARID proteins: a diverse family of DNA binding proteins implicated in the control of cell growth, differentiation, and development.

  2002cited by this paper
• Histone acetylation regulates the time of replication origin firing.

  2002cited by this paper
• The yeast CDK inhibitor Sic1 prevents genomic instability by promoting replication origin licensing in late G(1).

  2002influential reference
• The ATM–Chk2–Cdc25A checkpoint pathway guards against radioresistant DNA synthesis

  2001cited by this paper
• Translating the Histone Code

  2001cited by this paper
• Activation of mammalian Chk1 during DNA replication arrest

  2001cited by this paper
• Nuclear organization of DNA replication in primary mammalian cells.

  2000cited by this paper
• Cell-cycle checkpoint kinases: checking in on the cell cycle.

  2000cited by this paper
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  2000cited by this paper
• Rapid destruction of human Cdc25A in response to DNA damage.

  2000cited by this paper
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  2000cited by this paper
• Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine.

  1999cited by this paper
• Formation of a preinitiation complex by S-phase cyclin CDK-dependent loading of Cdc45p onto chromatin.

  1998influential reference
• Dynamic molecular combing: stretching the whole human genome for high-resolution studies.

  1997cited by this paper
• Isolation and characterization of XE169, a novel human gene that escapes X-inactivation.

  1994cited by this paper
• A question of time: replication origins of eukaryotic chromosomes.

  1992cited by this paper
• Nucleosome positioning can affect the function of a cis-acting DMA elementin vivo

  1990cited by this paper
• Mapping replicational sites in the eucaryotic cell nucleus

  1989cited by this paper
• Coordinated leading and lagging strand synthesis during SV40 DNA replication in vitro requires PCNA.

  1988cited by this paper
• Functional identity of proliferating cell nuclear antigen and a DNA polymerase-δ auxiliary protein

  1987cited by this paper
• "Systematic"

  1966cited by this paper

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