Hierarchical Assembly and Disassembly of a Transcriptionally Active RAG Locus in CD4CD8 Thymocytes

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2018 Dec 15

PMID 30545902

Citations 16

Authors

Abani Kanta Naik

Aaron T Byrd

Aaron C K Lucander

Michael S Krangel

Affiliations

Soon will be listed here.

Abstract

Expression of and is tightly regulated in developing T cells to mediate TCR gene assembly. Here we have investigated the molecular mechanisms governing the assembly and disassembly of a transcriptionally active RAG locus chromatin hub in CD4CD8 thymocytes. and gene expression in CD4CD8 thymocytes depends on and promoter activation by a distant antisilencer element (ASE). We identify GATA3 and E2A as critical regulators of the ASE, and Runx1 and E2A as critical regulators of the promoter. We reveal hierarchical assembly of a transcriptionally active chromatin hub containing the ASE and RAG promoters, with recruitment and expression dependent on assembly of a functional ASE- framework. Finally, we show that signal-dependent down-regulation of RAG gene expression in CD4CD8 thymocytes depends on Ikaros and occurs with disassembly of the RAG locus chromatin hub. Our results provide important new insights into the molecular mechanisms that orchestrate RAG gene expression in developing T cells.

Citing Articles

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