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Updated: May 4, 2026
Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
Published on: January 26, 2018
The demethylase JMJD2C localizes to H3K4me3-positive transcription start sites and is dispensable for embryonic
Marianne Terndrup Pedersen1, Karl Agger, Anne Laugesen
1Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Abstract:
The histone demethylase JMJD2C, also known as KDM4C/GASC1, has activity against methylated H3K9 and H3K36 and is amplified and/or overexpressed in human cancers. By the generation of Jmjd2c knockout mice, we demonstrate that loss of Jmjd2c is compatible with cellular proliferation, embryonic stem cell (ESC) self-renewal, and embryonic development. Moreover, we report that JMJD2C localizes to H3K4me3-positive transcription start sites in both primary cells and in the human carcinoma KYSE150 cell line containing an amplification of the JMJD2C locus. Binding is dependent on the double Tudor domain of JMJD2C, which recognizes H3K4me3 but not H4K20me2/me3 in vitro, showing a binding specificity different from that of the double Tudor domains of JMJD2A and JMJD2B. Depletion of JMJD2C in KYSE150 cells has a modest effect on H3K9me3 and H3K36me3 levels but impairs proliferation and leads to deregulated expression of a subset of target genes involved in cell cycle progression. Taking these findings together, we show that JMJD2C is targeted to H3K4me3-positive transcription start sites, where it can contribute to transcriptional regulation, and report that the putative oncogene JMJD2C generally is not required for cellular proliferation or embryonic development.
Insights
The histone demethylase JMJD2C (KDM4C) is often overexpressed in cancers. Loss of JMJD2C does not impede cell proliferation or development, suggesting it is not essential for these processes.
Area of Science:
- Epigenetics
- Molecular Biology
- Cancer Biology
Background:
- The histone demethylase JMJD2C (KDM4C/GASC1) targets methylated H3K9 and H3K36.
- JMJD2C is amplified and/or overexpressed in human cancers, implicating it as a potential oncogene.
Purpose of the Study:
- To investigate the role of JMJD2C in cellular proliferation, embryonic development, and gene regulation.
- To determine the binding specificity and localization of JMJD2C in cancer cells.
Main Methods:
- Generation of Jmjd2c knockout mice.
- Analysis of JMJD2C localization and binding to histone modifications (H3K4me3, H4K20me2/me3) using in vitro assays.
- Depletion of JMJD2C in human carcinoma KYSE150 cells and assessment of proliferation and gene expression changes.
Main Results:
- Loss of Jmjd2c is compatible with cellular proliferation, embryonic stem cell self-renewal, and embryonic development.
- JMJD2C localizes to H3K4me3-positive transcription start sites, with binding dependent on its double Tudor domain.
- JMJD2C exhibits binding specificity for H3K4me3, distinct from JMJD2A and JMJD2B.
- Depletion of JMJD2C in KYSE150 cells impairs proliferation and deregulates a subset of cell cycle-related genes, with modest effects on H3K9me3 and H3K36me3 levels.
Conclusions:
- JMJD2C is targeted to H3K4me3-marked transcription start sites and contributes to transcriptional regulation.
- Despite its oncogenic potential, JMJD2C is generally not required for cellular proliferation or embryonic development.
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