TCF-1 promotes chromatin interactions across topologically associating domains in T cell progenitors.

TCF-1 promotes chromatin interactions across topologically associating domains in T cell progenitors.
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TCF-1促进T细胞祖细胞中拓扑相关结构域之间的染色质相互作用。

DOI:
10.1038/s41590-022-01232-z
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发表时间:
2022-07
期刊:
影响因子:
30.5
通讯作者:
Vahedi, Golnaz
Vahedi, Golnaz
中科院分区:
医学1区
文献类型:
--
作者:
Wang, Wenliang;Chandra, Aditi;Goldman, Naomi;Yoon, Sora;Ferrari, Emily K.;Nguyen, Son. C.;Joyce, Eric F.;Vahedi, Golnaz

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高迁移率族(HMG)转录因子TCF-1是早期T细胞发育所必需的。尽管体外生化分析表明HMG蛋白可以作为高级核组织组装中的结构元件,但TCF-1在T细胞发育过程中对三维(3D)基因组结构控制的贡献仍然未知。在这里,我们研究了TCF-1在3D基因组重构中的作用。使用功能获得和丧失实验,我们发现TCF-1和结构蛋白CTCF的共占据改变了T细胞祖细胞中拓扑相关结构域的结构,导致先前绝缘的调控元件和靶基因在T细胞发育的后期阶段之间的相互作用。TCF-1依赖性增益在远程相互作用中与活性增强子标记H3 K27 ac的沉积和在活性增强子处的粘附素加载因子NIPBL的募集有关。这些数据表明,TCF-1在T细胞发育过程中控制全球基因组组织中发挥作用。
The high mobility group (HMG) transcription factor TCF-1 is essential for early T cell development. Although in vitro biochemical assays suggest that HMG proteins can serve as architectural elements in the assembly of higher-order nuclear organization, the contribution of TCF-1 on the control of three-dimensional (3D) genome structures during T cell development remains unknown. Here, we investigated the role of TCF-1 in 3D genome reconfiguration. Using gain and loss of function experiments, we discovered that the co-occupancy of TCF-1 and the architectural protein CTCF altered the structure of topologically associating domains in T cell progenitors, leading to interactions between previously insulated regulatory elements and target genes at late stages of T cell development. The TCF-1 dependent gain in long-range interactions was linked to deposition of active enhancer mark H3K27ac and recruitment of the cohesin-loading factor NIPBL at active enhancers. These data indicate that TCF-1 has a role in controlling the global genome organization during T cell development.
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