title: Fine-tuning of epigenetic regulation with respect to promoter CpG content in a cell type-specific manner.
abstract: Epigenetic regulation of gene expression is fundamental for cell type-specific gene expression. However, integrated comparative transcriptomic and epigenomic analyses in various adult primary differentiated cells remain underrepresented. We generated promoter landscapes of DNA methylation and three important histone methylation marks (H3K4me3, H3K9me2, and H3K27me3) in two primary cell types (B lymphocytes and liver) from adult mice. In line with previous studies, we also observed distinct H3K4me3 patterns at promoters dictated by CpG content in differentiated primary cells. We further explored the distribution of initiating RNA polymerase II and elongating RNA polymerase II across genes within different promoter classes, suggesting different rate-limiting steps at CpG-rich vs. CpG-poor genes. Examination of differentially expressed genes revealed that regulation of tissue-specific genes is closely related to gene function regardless of promoter type. Although repressive chromatin marks displayed differential preference to promoters based on CpG content, we observed fine-tuning of the pattern of association of these marks with specific promoter types in a cell type-specific manner. The distribution of H3K9me2 and H3K27me3, relative to CpG content, differed substantially between the two cell types. Cell-type specific accumulation of repressive chromatin marks was also observed at silent genes in both cell types, suggesting that differentiated primary cells may exhibit cell-type specificity in the distribution of repressive chromatin marks. Epigenetic regulation of gene expression and the association of specific histone marks with promoter sequence classes are fine-tuned in a cell type-specific manner. This unexpected finding underscores the value of extensive study of epigenetic marks across cell and tissue types.
authors: Laboratory of Molecular Carcinogenesis; National Institute of Environmental Health Sciences; Research Triangle Park, NC USA.
authors: Ruifang
authors: R
authors: Li
authors: SRA International; Research Triangle Park, NC USA.
authors: Deepak
authors: D
authors: Mav
authors: Integrative Bioinformatics; National Institute of Environmental Health Sciences; Research Triangle Park, NC USA.
authors: Sara A
authors: SA
authors: Grimm
authors: Laboratory of Molecular Carcinogenesis; National Institute of Environmental Health Sciences; Research Triangle Park, NC USA; Biostatistics Branch; National Institute of Environmental Health Sciences; Research Triangle Park, NC USA.
authors: Raja
authors: R
authors: Jothi
authors: SRA International; Research Triangle Park, NC USA.
authors: Ruchir
authors: R
authors: Shah
authors: Laboratory of Molecular Carcinogenesis; National Institute of Environmental Health Sciences; Research Triangle Park, NC USA.
authors: Paul A
authors: PA
authors: Wade
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism
chemical_list: D006657:Histones; D012319:RNA Polymerase II
keywords: CpG content; CpG island; epigenetics; promoter; transcription regulation