Chromatin organizer SATB1 controls the cell identity of CD4+ CD8+ double-positive thymocytes by regulating the activity of super-enhancers

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Sept. 22, 2022

Abstract CD4 + and CD8 double-positive (DP) thymocytes play a crucial role in T cell development the thymus. DP cells rearrange receptor gene Tcra to generate receptors with TCRβ. differentiate into or single-positive (SP) thymocytes, regulatory cells, invariant nature kill (iNKT) response TCR signaling. Chromatin organizer SATB1 is highly expressed essential regulating rearrangement differentiation of cells. Here we explored mechanism orchestrating expression Single-cell RNA sequencing shows that Satb1 deletion changes identity down-regulates genes specifically Super-enhancers regulate expressions DP-specific genes, our Hi-C data show deficiency reduces super-enhancer activity by decreasing interactions among super-enhancers between promoters. Our results reveal plays critical thymocyte promote establishment globally at chromatin architectural level.

Language: Английский

SATB1 regulates 3D genome architecture in T cells by constraining chromatin interactions surrounding CTCF-binding sites

Cell Reports, Journal Year: 2023, Volume and Issue: 42(4), P. 112323 - 112323

Published: March 30, 2023

Special AT-rich sequence binding protein 1 (SATB1) has long been proposed to act as a global chromatin loop organizer in T cells. However, the exact functions of SATB1 spatial genome organization remain elusive. Here we show that depletion human and murine cells leads transcriptional dysregulation for genes involved cell activation, well alterations 3D architecture at multiple levels, including compartments, topologically associating domains, loops. Importantly, extensively colocalizes with CTCF throughout genome. Depletion increased contacts among across SATB1/CTCF co-occupied sites, thereby affecting transcription critical regulators activation. The loss does not affect occupancy but significantly reduces retention nuclear matrix. Collectively, our data contributes by constraining topology surrounding CTCF-binding sites.

Language: Английский

Organizational principles of integumentary Organs: Maximizing Variations for Effective Adaptation

Developmental Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский