Abstract

Transcriptional programs are controlled by the interplay between DNA sequence, transcription factors, and epigenetic mechanisms. We report genome-wide characterization of GATA3 binding sites in eleven well-defined developmental and effector cell types of the T lymphocyte lineage. By utilizing a conditional allele of Gata3, we investigated the impact of GATA3 expression on the mRNA expression patterns in several of these cell types. Correlation of GATA3 binding with gene expression changes indicates that GATA3 regulates a large number of stage- and cell-specific genes involved in multiple signaling and transcriptional pathways critical for T cell differentiation and immune responses. In addition to a primary GATA motif, GATA3 recruitment to a significant fraction of target sites may be mediated by secondary motifs depending on cellular context, suggesting a mechanism of expanding the regulatory complexity of a limited number of sequence-specific transcription factors. We show that GATA3 mediates H3K27me3 and H3K4 methylation to facilitate transcriptional repression or activation, respectively.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL006030-03
Application #
8344839
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2011
Total Cost
$506,773
Indirect Cost

  Institution

Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Baranello, Laura; Kouzine, Fedor; Wojtowicz, Damian et al. (2018) Mapping DNA Breaks by Next-Generation Sequencing. Methods Mol Biol 1672:155-166
Yohe, Marielle E; Gryder, Berkley E; Shern, Jack F et al. (2018) MEK inhibition induces MYOG and remodels super-enhancers in RAS-driven rhabdomyosarcoma. Sci Transl Med 10:
He, Yanghua; Zuo, Qisheng; Edwards, John et al. (2018) DNA Methylation and Regulatory Elements during Chicken Germline Stem Cell Differentiation. Stem Cell Reports 10:1793-1806
Hodges, H Courtney; Stanton, Benjamin Z; Cermakova, Katerina et al. (2018) Dominant-negative SMARCA4 mutants alter the accessibility landscape of tissue-unrestricted enhancers. Nat Struct Mol Biol 25:61-72
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
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
Cooper, James; Ding, Yi; Song, Jiuzhou et al. (2017) Genome-wide mapping of DNase I hypersensitive sites in rare cell populations using single-cell DNase sequencing. Nat Protoc 12:2342-2354
Ren, Gang; Jin, Wenfei; Cui, Kairong et al. (2017) CTCF-Mediated Enhancer-Promoter Interaction Is a Critical Regulator of Cell-to-Cell Variation of Gene Expression. Mol Cell 67:1049-1058.e6
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
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

Showing the most recent 10 out of 58 publications