Transcription Factor YY1 is Essential for Regulation of the Th2 Cytokine Locus and for Th2 Cell Differentiation

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2012 Dec 19

PMID 23248301

Citations 52

Authors

Soo Seok Hwang

Young Uk Kim

Sumin Lee

Sung Woong Jang

Min Kyung Kim

Byung Hee Koh

Wonyong Lee

Joomyeong Kim

Abdallah Souabni

Meinrad Busslinger

Gap Ryol Lee

Affiliations

Soon will be listed here.

Abstract

The Th2 locus control region (LCR) has been shown to be important in efficient and coordinated cytokine gene regulation during Th2 cell differentiation. However, the molecular mechanism for this is poorly understood. To study the molecular mechanism of the Th2 LCR, we searched for proteins binding to it. We discovered that transcription factor YY1 bound to the LCR and the entire Th2 cytokine locus in a Th2-specific manner. Retroviral overexpression of YY1 induced Th2 cytokine expression. CD4-specific knockdown of YY1 in mice caused marked reduction in Th2 cytokine expression, repressed chromatin remodeling, decreased intrachromosomal interactions, and resistance in an animal model of asthma. YY1 physically associated with GATA-binding protein-3 (GATA3) and is required for GATA3 binding to the locus. YY1 bound to the regulatory elements in the locus before GATA3 binding. Thus, YY1 cooperates with GATA3 and is required for regulation of the Th2 cytokine locus and Th2 cell differentiation.

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