Abstract

The human genome is organized in a highly ordered DNA-histone complex that is subject to a variety of developmentally regulated covalent modifications to constitute a specific epigenome. The post-translational modifications of histones play critical roles in regulating genome-wide gene expression program. We have generated the first comprehensive epigenomic map of human T cells for the major histone modifications including diacetylation of histone H3 lysines 9 and 14 (H3K9acK14ac), trimethylation of H3 lysine 4 (H3K4me3), trimethylation of H3 lysine 9 (H3K9me3), and trimethylation of H3 lysine 27 (H3K27me3). Our data indicate that a large number of human genes are regulated by a complex combinatorial usage of both active and repressive epigenetic marks. Moreover, using the epigenomic map, we have identified for the first time human Polycomb Response Elements (PREs), which are critical cis-elements to mediate the activities of PcG proteins. We show that these human PREs are associated with both PRC1 and PRC2 proteins in vivo. The transcriptional repression of reporter genes by the human PREs requires the presence of the epigenetic mark, H3K27me3, and PcG proteins. Furthermore, we demonstrate that human PREs function as bona fide PREs in Drosophila, implying that not only the trans PcG proteins but also certain features of the cis PREs are well conserved. Our data suggest that similar mechanisms are used in targeting the PcG proteins for transcriptional silencing in Drosophila and mammals.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Intramural Research (Z01)
Project #
1Z01HL005801-04
Application #
7321639
Study Section
(LA)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2006
Total Cost
Indirect Cost

  Institution

Name
U.S. National Heart Lung and Blood Inst
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Kraushaar, Daniel C; Chen, Zuozhou; Tang, Qingsong et al. (2018) The gene repressor complex NuRD interacts with the histone variant H3.3 at promoters of active genes. Genome Res 28:1646-1655
Hu, Gangqing; Cui, Kairong; Northrup, Daniel et al. (2013) H2A.Z facilitates access of active and repressive complexes to chromatin in embryonic stem cell self-renewal and differentiation. Cell Stem Cell 12:180-92
Guo, Liying; Wei, Gang; Zhu, Jinfang et al. (2009) IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1 cells. Proc Natl Acad Sci U S A 106:13463-8
Chepelev, Iouri; Wei, Gang; Tang, Qingsong et al. (2009) Detection of single nucleotide variations in expressed exons of the human genome using RNA-Seq. Nucleic Acids Res 37:e106
Zhu, Jinfang; Davidson, Todd S; Wei, Gang et al. (2009) Down-regulation of Gfi-1 expression by TGF-beta is important for differentiation of Th17 and CD103+ inducible regulatory T cells. J Exp Med 206:329-41
Lin, Biaoyang; Wang, Jun; Hong, Xu et al. (2009) Integrated expression profiling and ChIP-seq analyses of the growth inhibition response program of the androgen receptor. PLoS One 4:e6589
Cuddapah, Suresh; Jothi, Raja; Schones, Dustin E et al. (2009) Global analysis of the insulator binding protein CTCF in chromatin barrier regions reveals demarcation of active and repressive domains. Genome Res 19:24-32
Zang, Chongzhi; Schones, Dustin E; Zeng, Chen et al. (2009) A clustering approach for identification of enriched domains from histone modification ChIP-Seq data. Bioinformatics 25:1952-8
Wang, Zhibin; Zang, Chongzhi; Rosenfeld, Jeffrey A et al. (2008) Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet 40:897-903
Schones, Dustin E; Cui, Kairong; Cuddapah, Suresh et al. (2008) Dynamic regulation of nucleosome positioning in the human genome. Cell 132:887-98

Showing the most recent 10 out of 27 publications