title: Relationship between gene body DNA methylation and intragenic H3K9me3 and H3K36me3 chromatin marks.
abstract: To elucidate the relationship between intragenic DNA methylation and chromatin marks, we performed epigenetic profiling of chromosome 19 in human bronchial epithelial cells (HBEC) and in the colorectal cancer cell line HCT116 as well as its counterpart with double knockout of DNMT1 and DNMT3B (HCT116-DKO). Analysis of H3K36me3 profiles indicated that this intragenic mark of active genes is associated with two categories of genes: (i) genes with low CpG density and H3K9me3 in the gene body or (ii) genes with high CpG density and DNA methylation in the gene body. We observed that a combination of low CpG density in gene bodies together with H3K9me3 and H3K36me3 occupancy is a specific epigenetic feature of zinc finger (ZNF) genes, which comprise 90% of all genes carrying both histone marks on chromosome 19. For genes with high intragenic CpG density, transcription and H3K36me3 occupancy were not changed in conditions of partial or intensive loss of DNA methylation in gene bodies. siRNA knockdown of SETD2, the major histone methyltransferase responsible for production of H3K36me3, did not reduce DNA methylation in gene bodies. Our study suggests that the H3K36me3 and DNA methylation marks in gene bodies are established largely independently of each other and points to similar functional roles of intragenic DNA methylation and intragenic H3K9me3 for CpG-rich and CpG-poor genes, respectively.
authors.affiliation: Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, California, United States of America.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Hahn
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.forename: Arthur X
authors.initials: AX
authors.lastname: Li
authors.forename: Torsten
authors.initials: T
authors.lastname: Hahn
authors.forename: Gerd P
authors.initials: GP
authors.lastname: Pfeifer
mesh_terms: D001980:Bronchi / Q000166:cytology; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D016000:Cluster Analysis; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000172:deficiency / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000378:metabolism; D055785:Gene Knockdown Techniques; D055786:Gene Knockout Techniques; D045325:HCT116 Cells; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D015533:Transcriptional Activation; D016335:Zinc Fingers / Q000235:genetics; D000097584:DNA Methyltransferase 3B
chemical_list: D002843:Chromatin; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones; D008239:Lysine; D000097584:DNA Methyltransferase 3B; C000619380:DNMT1 protein, human; C521636:SETD2 protein, human