SATB1 regulates 3D genome architecture in T cells by constraining chromatin interactions surrounding CTCF-binding sites.
SATB1 regulates 3D genome architecture in T cells by constraining chromatin interactions surrounding CTCF-binding sites.
复制标题
DOI：
10.1016/j.celrep.2023.112323
复制
发表时间：
2023-03
期刊：
影响因子：
8.8
通讯作者：
Bao Wang;Luzhang Ji;Q. Bian
中科院分区：
文献类型：
--
作者：
Bao Wang;Luzhang Ji;Q. Bian
特异性富含AT序列结合蛋白1（SATB 1）长期以来被认为是T细胞中的一个全局染色质环组织者。然而，SATB 1在空间基因组组织中的确切功能仍然难以捉摸。在这里，我们表明，在人类和小鼠T细胞中SATB 1的耗尽导致转录失调的基因参与T细胞活化，以及在多个水平上的3D基因组结构的改变，包括区室，拓扑相关的结构域，和环。重要的是，SATB 1在整个基因组中与CTCF广泛共定位。SATB 1的消耗导致SATB 1/CTCF共占据位点之间和跨SATB 1/CTCF共占据位点的染色质接触增加，从而影响T细胞活化的关键调节因子的转录。SATB 1的丢失不影响CTCF的占有率，但显著降低了CTCF在核基质中的保留。总的来说，我们的数据表明，SATB 1有助于3D基因组组织通过限制周围CTCF结合位点的染色质拓扑结构。
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 in spatial genome organization remain elusive. Here we show that the depletion of SATB1 in human and murine T cells leads to transcriptional dysregulation for genes involved in T cell activation, as well as alterations of 3D genome architecture at multiple levels, including compartments, topologically associating domains, and loops. Importantly, SATB1 extensively colocalizes with CTCF throughout the genome. Depletion of SATB1 leads to increased chromatin contacts among and across the SATB1/CTCF co-occupied sites, thereby affecting the transcription of critical regulators of T cell activation. The loss of SATB1 does not affect CTCF occupancy but significantly reduces the retention of CTCF in the nuclear matrix. Collectively, our data show that SATB1 contributes to 3D genome organization by constraining chromatin topology surrounding CTCF-binding sites.