Effect of induced conditional knockout of Satb1 in thymocyte subsets [RNA-seq]

Although factors such as CTCF have been extensively studied in the hierarchical regulation of 3D chromatin organization, the mechanisms driving dynamic genome folding during T cell fate transitions remain incompletely defined. In this study, we reveal that Satb1, a chromatin organizer enriched in the T cell lineage, co-occupies genomic regions with the cohesin complex and Ctcf in double-positive (DP) thymocytes, where chromatin interactions are notably increased.

We show that Satb1 physically interacts with the cohesin subunit Smc1a, and its deletion results in aberrant Smc1a binding and reduced chromatin contacts at sites co-occupied by Satb1 and cohesin. In both DP and immature CD4 single-positive (SP) T cells, Satb1 is essential for proper T cell activation and cytokine signaling. At the Cd3 locus, Satb1 and cohesin collaboratively regulate gene expression, with Satb1 loss leading to disrupted Smc1a occupancy and compromised chromatin interactions.