Recent epigenomic studies have predicted thousands of potential enhancers in the human genome. However, there has not been systematic characterization of target promoters for these potential enhancers. Using H3K4me2 as a mark for active enhancers, we identified genome-wide Enhancer-Promoter interactions in human CD4+ T cells using ChIA-PET. Among the 6 520 long- distance chromatin interactions, we identify 2 067 enhancers that interact with 1 619 promoters and enhance their expression. These enhancers exist in accessible chromatin regions and are associated with various histone modifications and polymerase II binding. The promoters with interacting enhancers are expressed at higher levels than those without interacting enhancers, and their expression levels are positively correlated with the number of interacting enhancers. Interestingly, interacting promoters are co-expressed in a tissue-specific manner. We also find that chromosomes are organized into multiple levels of interacting domains. Our results define a global view of EP interactions and provide a data set to further understand mechanisms of enhancer targeting and long-range chromatin organization.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2012
Total Cost
$603,602
Indirect Cost
Name
National Heart, Lung, and Blood Institute
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Placek, Katarzyna; Hu, Gangqing; Cui, Kairong et al. (2017) MLL4 prepares the enhancer landscape for Foxp3 induction via chromatin looping. Nat Immunol 18:1035-1045
Northrup, Daniel; Yagi, Ryoji; Cui, Kairong et al. (2017) Histone demethylases UTX and JMJD3 are required for NKT cell development in mice. Cell Biosci 7:25
Barski, Artem; Cuddapah, Suresh; Kartashov, Andrey V et al. (2017) Rapid Recall Ability of Memory T cells is Encoded in their Epigenome. Sci Rep 7:39785
Zhong, Chao; Cui, Kairong; Wilhelm, Christoph et al. (2016) Erratum: Group 3 innate lymphoid cells continuously require the transcription factor GATA-3 after commitment. Nat Immunol 17:469
Zhong, Chao; Cui, Kairong; Wilhelm, Christoph et al. (2016) Group 3 innate lymphoid cells continuously require the transcription factor GATA-3 after commitment. Nat Immunol 17:169-78
Ni, Ting; Yang, Wenjing; Han, Miao et al. (2016) Global intron retention mediated gene regulation during CD4+ T cell activation. Nucleic Acids Res 44:6817-29
Crompton, Joseph G; Narayanan, Manikandan; Cuddapah, Suresh et al. (2016) Lineage relationship of CD8(+) T cell subsets is revealed by progressive changes in the epigenetic landscape. Cell Mol Immunol 13:502-13
Zhong, Chao; Cui, Kairong; Wilhelm, Christoph et al. (2016) Erratum: Group 3 innate lymphoid cells continuously require the transcription factor GATA-3 after commitment. Nat Immunol 17:214
Hu, Gangqing; Zhao, Keji (2016) Looping around Bcl6 in Germinal Center to Sharpen B Cell Immunity. Immunity 45:459-61
Ren, Gang; Cui, Kairong; Zhang, Zhiying et al. (2015) Division of labor between IRF1 and IRF2 in regulating different stages of transcriptional activation in cellular antiviral activities. Cell Biosci 5:17

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