title: Natural variation in the histone demethylase, KDM4C, influences expression levels of specific genes including those that affect cell growth.
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.
authors.affiliation: VMD-PhD Program, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Brittany L
authors.initials: BL
authors.lastname: Gregory
authors.forename: Vivian G
authors.initials: VG
authors.lastname: Cheung
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D008040:Genetic Linkage; D014644:Genetic Variation; D006657:Histones / Q000378:metabolism*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000378:metabolism*; D008745:Methylation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype
chemical_list: D006657:Histones; C413655:KDM4C protein, human; D056484:Jumonji Domain-Containing Histone Demethylases