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Updated: Feb 11, 2026
13:20
Chromatin Immunoprecipitation ChIP to Assay Dynamic Histone Modification in Activated Gene Expression in Human Cells
Published on: July 29, 2010
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CTCF-KDM4A complex correlates with histone modifications that negatively regulate CHD5 gene expression in cancer cell
Lissania Guerra-Calderas1, Rodrigo González-Barrios1, Carlos César Patiño1
1Cancer Biomedical Research Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
Oncotarget
|April 24, 2018
Summary
The histone demethylase KDM4A and CTCF form a complex that represses the CHD5 gene by reducing H3K36me3/2 marks in its first intron, independent of promoter methylation.
Area of Science:
- Epigenetics
- Molecular Biology
- Cancer Biology
Background:
- Histone demethylase KDM4A targets H3K9me3 and H3K36me3 epigenetic marks.
- KDM4A is aberrantly expressed in cancer and influences target gene expression, including CHD5.
- CTCF enhances KDM4A's demethylase activity, but the repression mechanism of CHD5 by CTCF and KDM4A is unclear.
Purpose of the Study:
- To elucidate the mechanism of CHD5 gene repression mediated by CTCF and KDM4A.
- To investigate the role of KDM4A and CTCF in regulating H3K36me3/2 marks at the CHD5 gene locus.
Main Methods:
- Protein complex formation analysis between CTCF and KDM4A.
- Chromatin immunoprecipitation to assess histone modifications (H3K36me3/2) at the CHD5 gene.
- siRNA-mediated depletion of CTCF and KDM4A.
- CRISPR-Cas9 knockout of KDM4A.
- Analysis of CHD5 gene expression and promoter DNA methylation.
Main Results:
- CTCF and KDM4A form a complex recruited to the first intron of CHD5.
- This complex reduces H3K36me3/2 histone marks, leading to CHD5 transcriptional downregulation.
- Depletion of CTCF or KDM4A reactivates CHD5 expression.
- KDM4A knockout restores CHD5 expression and H3K36me3/2 marks.
- The repression mechanism is independent of CHD5 promoter DNA methylation.
Conclusions:
- CTCF and KDM4A collaborate to epigenetically repress the CHD5 gene via gene body histone modification.
- This study reveals a novel mechanism of gene repression acting at the gene body, distinct from promoter silencing.
- The findings highlight a new pathway for epigenetic regulation relevant to cancer biology.
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