Bcl11b, a Novel GATA3-interacting Protein, Suppresses Th1 While Limiting Th2 Cell Differentiation

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2018 Mar 9

PMID 29514917

Citations 31

Authors

Difeng Fang

Kairong Cui

Gangqing Hu

Rama Krishna Gurram

Chao Zhong

Andrew J Oler

Ryoji Yagi

Ming Zhao

Suveena Sharma

Pentao Liu

Bing Sun

Keji Zhao

Jinfang Zhu

Affiliations

Soon will be listed here.

Abstract

GATA-binding protein 3 (GATA3) acts as the master transcription factor for type 2 T helper (Th2) cell differentiation and function. However, it is still elusive how GATA3 function is precisely regulated in Th2 cells. Here, we show that the transcription factor B cell lymphoma 11b (Bcl11b), a previously unknown component of GATA3 transcriptional complex, is involved in GATA3-mediated gene regulation. Bcl11b binds to GATA3 through protein-protein interaction, and they colocalize at many important cis-regulatory elements in Th2 cells. The expression of type 2 cytokines, including IL-4, IL-5, and IL-13, is up-regulated in -deficient Th2 cells both in vitro and in vivo; such up-regulation is completely GATA3 dependent. Genome-wide analyses of Bcl11b- and GATA3-regulated genes (from RNA sequencing), cobinding patterns (from chromatin immunoprecipitation sequencing), and Bcl11b-modulated epigenetic modification and gene accessibility suggest that GATA3/Bcl11b complex is involved in limiting Th2 gene expression, as well as in inhibiting non-Th2 gene expression. Thus, Bcl11b controls both GATA3-mediated gene activation and repression in Th2 cells.

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