The Transcription Factor Runx3 Establishes Chromatin Accessibility of Cis-Regulatory Landscapes That Drive Memory Cytotoxic T Lymphocyte Formation

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2018 Apr 19

PMID 29669249

Citations 94

Authors

Dapeng Wang

Huitian Diao

Adam J Getzler

Walter Rogal

Megan A Frederick

Justin Milner

Bingfei Yu

Shane Crotty

Ananda W Goldrath

Matthew E Pipkin

Affiliations

Soon will be listed here.

Abstract

T cell receptor (TCR) stimulation of naive CD8 T cells initiates reprogramming of cis-regulatory landscapes that specify effector and memory cytotoxic T lymphocyte (CTL) differentiation. We mapped regions of hyper-accessible chromatin in naive cells during TCR stimulation and discovered that the transcription factor (TF) Runx3 promoted accessibility to memory CTL-specific cis-regulatory regions before the first cell division and was essential for memory CTL differentiation. Runx3 was specifically required for accessibility to regions highly enriched with IRF, bZIP and Prdm1-like TF motifs, upregulation of TFs Irf4 and Blimp1, and activation of fundamental CTL attributes in early effector and memory precursor cells. Runx3 ensured that nascent CTLs differentiated into memory CTLs by preventing high expression of the TF T-bet, slowing effector cell proliferation, and repressing terminal CTL differentiation. Runx3 overexpression enhanced memory CTL differentiation during iterative infections. Thus, Runx3 governs chromatin accessibility during TCR stimulation and enforces the memory CTL developmental program.

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