Conserved antagonism between JMJD2A/KDM4A and HP1γ during cell cycle progression
Joshua C Black1, Andrew Allen, Capucine Van Rechem
1Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, 13th Street, Charlestown, MA 02129, USA.
Molecular Cell
|December 15, 2010
Summary
Histone demethylase JMJD2A (KDM4A) regulates cell cycle progression and DNA replication. This conserved function involves controlling chromatin accessibility and antagonizing HP1γ, impacting cancer cell proliferation.
Area of Science:
- Epigenetics
- Molecular Biology
- Cell Biology
Background:
- The KDM4/JMJD2 family of histone demethylases is frequently amplified in human cancers.
- The specific physiological and oncogenic roles of JMJD2A/KDM4A remain largely uncharacterized.
Purpose of the Study:
- To investigate the role of JMJD2A/KDM4A in cell cycle progression and DNA replication.
- To elucidate the conserved mechanisms underlying JMJD2A/KDM4A function in eukaryotes.
Main Methods:
- Cell cycle analysis and chromatin accessibility assays in human cells.
- DNA replication timing studies using CRISPR/Cas9.
- Functional analysis of the C. elegans homolog JMJD-2, including DNA replication and apoptosis assays.
- Investigating the interaction between JMJD2A/KDM4A and HP1γ/HPL-2.
Main Results:
- JMJD2A protein levels are cell cycle-dependent, and its overexpression enhances chromatin accessibility and S phase progression.
- JMJD2A enzymatic activity is crucial for altering replication timing and promoting cell cycle progression.
- Depletion of C. elegans JMJD-2 impairs DNA replication and elevates apoptosis.
- HP1γ antagonizes JMJD2A-mediated S phase progression, and HPL-2 depletion rescues DNA replication defects in jmjd-2 mutants.
Conclusions:
- JMJD2A/KDM4A plays a conserved role in regulating DNA replication and cell cycle progression.
- JMJD2A/KDM4A functions by modulating chromatin accessibility and antagonizing HP1γ.
- This mechanism is critical for normal DNA replication and may have implications for cancer development.
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