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The 3D enhancer network of the developing T cell genome is controlled by SATB1

Authors :
Sören Franzenburg
Tomas Zelenka
Petros Tzerpos
Ioannis-Rafail Tzonevrakis
Dionysios-Alexandros Papamatheakis
Antonios Klonizakis
Charalampos G. Spilianakis
Despina Tsoukatou
Dariusz Plewczynski
Christoforos Nikolaou
Publication Year :
2021
Publisher :
Cold Spring Harbor Laboratory, 2021.

Abstract

SummaryMechanisms of tissue-specific gene expression regulation via spatial coordination of gene promoters and distal regulatory elements are still poorly understood. We investigated the 3D genome organization of developing murine T cells and identified SATB1, a tissue-specific genome organizer, enriched at the anchors of promoter-enhancer chromatin loops. We assessed the function of SATB1 in T cell chromatin organization and compared it to the conventional genome organizer CTCF. SATB1 builds a more refined layer of genome organization upon a CTCF scaffold. To understand the regulatory implications of SATB1 loopscape structure, we generatedSatb1fl/flCd4-Cre+(Satb1cKO) conditional knockout animals which suffered from autoimmunity. We aimed to identify molecular mechanisms responsible for the deregulation of the immune system inSatb1cKO animals. H3K27ac HiChIP and Hi-C experiments indicated that SATB1 primarily mediates promoter-enhancer loops affecting master regulator genes (such asBcl6), the T cell receptor locus and adhesion molecule genes, collectively being critical for cell lineage specification and immune system homeostasis. Our findings unravel the function of a tissue-specific factor that controls transcription programs, via spatial chromatin arrangements complementary to the chromatin structure imposed by ubiquitously expressed genome organizers.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........f7bcc85866d5264c9771fc536d36beff
Full Text :
https://doi.org/10.1101/2021.07.09.451769