The forkhead transcription factor FOXK2 premarks lineage-specific genes in human embryonic stem cells for activation during differentiation.
The forkhead transcription factor FOXK2 premarks lineage-specific genes in human embryonic stem cells for activation during differentiation.
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DOI：
10.1093/nar/gkaa1281
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发表时间：
2021-02-22
影响因子：
14.9
通讯作者：
Sharrocks AD
中科院分区：
文献类型：
--
作者：
Ji Z;Li Y;Liu SX;Sharrocks AD
增强子在发育过程中以精心设计的空间和时间方式控制基因表达方面发挥着重要作用。然而，目前尚不清楚这些调节区域在分化过程中是如何建立的。在这里，我们研究了人类胚胎干细胞 (ESC) 和下游细胞类型中叉头转录因子 FOXK2 的全基因组结合谱。该转录因子与人类 ESC 中的数千个调节区域结合，并且随着细胞分化为中内胚层和神经前体细胞 (NPC) 类型以及新结合区域的出现，许多位点的结合得以维持。 FOXK2 结合通常与任何给定细胞类型中的活性组蛋白标记相关。此外，新获得的或保留的 FOXK2 结合区在分化为 NPC 后显示出激活组蛋白标记水平升高。为了与激活标记的这种关联保持一致，我们证明了 FOXK 转录因子在 NPC 分化过程中基因激活中的作用。因此，FOXK2 在 ESC 中的占据是描绘调节区域的早期标志，这些区域在后来的谱系中被激活。
Enhancers play important roles in controlling gene expression in a choreographed spatial and temporal manner during development. However, it is unclear how these regulatory regions are established during differentiation. Here we investigated the genome-wide binding profile of the forkhead transcription factor FOXK2 in human embryonic stem cells (ESCs) and downstream cell types. This transcription factor is bound to thousands of regulatory regions in human ESCs, and binding at many sites is maintained as cells differentiate to mesendodermal and neural precursor cell (NPC) types, alongside the emergence of new binding regions. FOXK2 binding is generally associated with active histone marks in any given cell type. Furthermore newly acquired, or retained FOXK2 binding regions show elevated levels of activating histone marks following differentiation to NPCs. In keeping with this association with activating marks, we demonstrate a role for FOXK transcription factors in gene activation during NPC differentiation. FOXK2 occupancy in ESCs is therefore an early mark for delineating the regulatory regions, which become activated in later lineages.
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影响因子：
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作者：
Chen X;Ji Z;Webber A;Sharrocks AD
通讯作者：
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