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

Tomas Zelenka, Antonios Klonizakis, Despina Tsoukatou, Dionysios-Alexandros Papamatheakis, Sören Franzenburg, Petros Tzerpos, Ioannis-Rafail Tzonevrakis, George Papadogkonas, Manouela Kapsetaki, Christoforos Nikolaou, Dariusz Plewczynski and Charalampos Spilianakis ()
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Tomas Zelenka: University of Crete
Antonios Klonizakis: University of Crete
Despina Tsoukatou: Institute of Molecular Biology and Biotechnology—Foundation for Research and Technology Hellas
Dionysios-Alexandros Papamatheakis: University of Crete
Sören Franzenburg: University Hospital Schleswig Holstein
Petros Tzerpos: University of Crete
Ioannis-Rafail Tzonevrakis: University of Crete
George Papadogkonas: University of Crete
Manouela Kapsetaki: Institute of Molecular Biology and Biotechnology—Foundation for Research and Technology Hellas
Christoforos Nikolaou: University of Crete
Dariusz Plewczynski: Warsaw University of Technology
Charalampos Spilianakis: University of Crete

Nature Communications, 2022, vol. 13, issue 1, 1-22

Abstract: Abstract Mechanisms of tissue-specific gene expression regulation via 3D genome organization are poorly understood. Here we uncover the regulatory chromatin network of developing T cells and identify SATB1, a tissue-specific genome organizer, enriched at the anchors of promoter-enhancer loops. We have generated a T-cell specific Satb1 conditional knockout mouse which allows us to infer the molecular mechanisms responsible for the deregulation of its immune system. H3K27ac HiChIP and Hi-C experiments indicate that SATB1-dependent promoter-enhancer loops regulate expression of master regulator genes (such as Bcl6), the T cell receptor locus and adhesion molecule genes, collectively being critical for cell lineage specification and immune system homeostasis. SATB1-dependent regulatory chromatin loops represent a more refined layer of genome organization built upon a high-order scaffold provided by CTCF and other factors. Overall, 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.

Date: 2022
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DOI: 10.1038/s41467-022-34345-y

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