Natural variation in the histone demethylase, KDM4C, influences expression levels of specific genes including those that affect cell growth
- 1VMD-PhD Program, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania 19104, USA;
- 2Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 3Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA;
- 4Department of Genetics,
- 5Department of Pediatrics, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104, USA
Abstract
DNA sequence variants influence gene expression and cellular phenotypes. In this study, we focused on natural variation in the gene encoding the histone demethylase, KDM4C, which promotes transcriptional activation by removing the repressive histone mark, H3K9me3, from its target genes. We uncovered cis-acting variants that contribute to extensive individual differences in KDM4C expression. We also identified the target genes of KDM4C and demonstrated that variation in KDM4C expression leads to differences in the growth of normal and some cancer cells. Together, our results from genetic mapping and molecular analysis provide an example of how genetic variation affects epigenetic regulation of gene expression and cellular phenotype.
Footnotes
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↵6 Corresponding author
E-mail vgcheung{at}umich.edu
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.156141.113.
- Received February 8, 2013.
- Accepted September 20, 2013.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
