Genome-wide analyses of GATA3-mediated gene regulation in distinct T cell types

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NHLBI	EPIGEN/TRANS/CHROM-13

* FARE Award Winner

Authors

• G Wei
• BJ Abraham
• R Yagi
• R Jothi
• K Cui
• S Sharma
• L Narlikar
• DN Northrup
• Q Tang
• WE Paul
• J Zhu
• K Zhao

Abstract

Transcription factor GATA3 is the master regulator of the T-helper 2 (Th2) subset of CD4+ T cells. GATA3 binds and regulates Interleukins 5 and 13, two Th2 signature cytokines. While Gata3 is expressed in all CD4+ effector lineages, it is unknown what genes GATA3 binds or regulates in non-Th2 subsets. To elucidate the roles of GATA3 and its mechanisms for regulating differentiation, we performed GATA3 ChIP-Seq in six T lymphocyte lineages, and RNA sequencing of these lineages in wild type/Gata3-knockout pairs. Gata3 knockout-induced differential expression consisted of lineage-specific activation and repression indicating complex roles for GATA3 in developmental transcription networks. Differentially expressed genes in Gata3-knockout cells preferentially occurred in immune gene interaction networks. Besides the WGATAR motif in GATA3-binding sites, we found other motifs in different lineages, suggesting a role for co-factors in GATA3 binding. Histone methylation around GATA3-binding sites showed widespread changes in Gata3-knockout cells. We observed a decrease of H3K4 methylation around GATA3-binding sites after Gata3 deletion. GATA3-bound and –activated genes showed a decrease in the activating H3K4me mark and an increase in the repressive H3K27me mark. These results indicate a role for GATA3 in chromatin organization and that this may explain GATA3 regulation of target gene expression.

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