Abstract

Histone modifications are implicated in influencing gene expression. To map the human epigenomes at high resolution, we have developed a technique termed ChIP-Seq by combining the chromatin immunoprecipitation assays (ChIP) with the Solexa 1G high throughput sequencing technology. We have generated high-resolution maps for the genome-wide distribution of 20 histone lysine and arginine methylations as well as histone variant H2A.Z, RNA polymerase II and the insulator binding protein CTCF across the human genome using ChIP-Seq. Typical patterns of histone methylations exhibited at promoters, insulators, enhancers and transcribed regions are identified. The monomethylation of H3K27, H3K9, H4K20, H3K79 and H2BK5 are all linked to gene activation, whereas trimethylation of H3K27, H3K9 and H3K79 are linked to repression. H2A.Z associates with functional regulatory elements and CTCF marks boundaries of histone methylation domains. Chromosome banding patterns are correlated with unique patterns of histone modifications. Chromosome breakpoints detected in T cell cancers frequently reside in chromatin regions associated with H3K4 methylations. Our data provide new insights into the function of histone methylation and chromatin organization in genome function.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Intramural Research (Z01)
Project #
1Z01HL005801-05
Application #
7594449
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2007
Total Cost
$2,819,235
Indirect Cost

  Institution

Name
National Heart, Lung, and Blood Institute
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
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
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
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