title: Global mapping of H3K4me1 and H3K4me3 reveals the chromatin state-based cell type-specific gene regulation in human Treg cells.
abstract: Regulatory T cells (Treg) contribute to the crucial immunological processes of self-tolerance and immune homeostasis. Genomic mechanisms that regulate cell fate decisions leading to Treg or conventional T cells (Tconv) lineages and those underlying Treg function remain to be fully elucidated, especially at the histone modification level. We generated high-resolution genome-wide distribution maps of monomethylated histone H3 lysine 4 (H3K4me1) and trimethylated H3K4 (H3K4me3) in human CD4(+)CD25(+)FOXP3(+) Tregs and CD4(+)CD25(+)FOXP3(-) activated (a)Tconv cells by DNA sequencing-by-synthesis. 2115 H3K4me3 regions corresponded to proximal promoters; in Tregs, the genes associated with these regions included the master regulator FOXP3 and the chemokine (C-C motif) receptor 7 (CCR7). 41024 Treg-specific H3K4me1 regions were identified. The majority of the H3K4me1 regions differing between Treg and aTconv cells were located at promoter-distal sites, and in vitro reporter gene assays were used to evaluate and identify novel enhancer activity. We provide for the first time a comprehensive genome-wide dataset of lineage-specific H3K4me1 and H3K4me3 patterns in Treg and aTconv cells, which may control cell type-specific gene regulation. This basic principle is likely not restricted to the two closely-related T cell populations, but may apply generally to somatic cell lineages in adult organisms.
authors: Institute of Immunology, PLA, Third Military Medical University, Chongqing, People's Republic of China.
authors: Yi
authors: Y
authors: Tian
authors: Zhengcai
authors: Z
authors: Jia
authors: Jun
authors: J
authors: Wang
authors: Zemin
authors: Z
authors: Huang
authors: Jun
authors: J
authors: Tang
authors: Yanhua
authors: Y
authors: Zheng
authors: Yan
authors: Y
authors: Tang
authors: Qinghong
authors: Q
authors: Wang
authors: Zhiqiang
authors: Z
authors: Tian
authors: Di
authors: D
authors: Yang
authors: Yi
authors: Y
authors: Zhang
authors: Xiaolan
authors: X
authors: Fu
authors: Jianxun
authors: J
authors: Song
authors: Shunli
authors: S
authors: Liu
authors: Jennifer C
authors: JC
authors: van Velkinburgh
authors: Yuzhang
authors: Y
authors: Wu
authors: Bing
authors: B
authors: Ni
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D002469:Cell Separation; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004742:Enhancer Elements, Genetic / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D015894:Genome, Human / Q000235:genetics; D006657:Histones / Q000378:metabolism*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; D002843:Chromatin; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006657:Histones; D053645:Interleukin-2 Receptor alpha Subunit; D008239:Lysine