The 3D enhancer network of the developing T cell genome is controlled by SATB1 [Hi-C]

ABSTRACT: Mechanisms of tissue-specific gene expression regulation, particularly via spatial coordination of gene promoters and their regulatory elements are poorly understood. Here we investigated the 3D genome organization of developing murine T cells. We identified a tissue-specific genome organizer SATB1 as a factor enriched at the anchors of promoter-enhancer chromatin loops. To unravel its functions in T cells, we generated Satb1fl/flCd4-Cre+ (Satb1 cKO) conditional knockout animals. Satb1 cKO animals suffer from severe autoimmunity so we sought to investigate a potential link between the autoimmunity and putatively deregulated nuclear architecture caused by SATB1 depletion. This series of Hi-C and HiChIP experiments is a part of SuperSeries including also RNA-Seq and ATAC-Seq experiments to fully understand the deregulation of Satb1 cKO thymocytes and to unravel the roles of SATB1 in T cell chromatin organization. Utilizing the HiChIP data, we compared SATB1 and CTCF-mediated chromatin loops, revealing that SATB1 builds a more refined layer of genome organization upon the CTCF scaffold. Moreover, H3K27ac HiChIP and Hi-C experiments in WT and Satb1 cKO thymocytes helped us to assess the functional impact of SATB1 and its underlying genome-wide regulome. SATB1 primarily mediates promoter-enhancer loops affecting a number of master regulator genes whose deregulation in knockout animals may comprise a cell-intrinsic mechanism of the autoimmunity. Our findings indicate a possible existence of a special class of genome organizers controlling tissue and/or time-specific transcriptional programs via spatial chromatin arrangements that are complementary to the function of conventional ubiquitously expressed genome organizers.

ORGANISM(S): Mus musculus

PROVIDER: GSE173446 | GEO | 2022/09/23

REPOSITORIES: GEO