UTX/KDM6A is known to interact and influence multiple different chromatin modifiers to promote an open chromatin environment to facilitate gene activation, but its molecular activities in developmental gene regulation remain unclear. We report that in human neural stem cells, UTX binding correlates with both promotion and suppression of gene expression. These activities enable UTX to modulate neural stem cell self-renewal, promote neurogenesis, and suppress gliogenesis. In neural stem cells, UTX has a less influence over histone H3 lysine 27 and lysine 4 methylation but more predominantly affects histone H3 lysine 27 acetylation and chromatin accessibility. Furthermore, UTX suppresses components of AP-1 and, in turn, a gliogenesis program. Our findings revealed that UTX coordinates dualistic gene regulation to govern neural stem cell properties and neurogenesis–gliogenesis switch.

中文翻译：

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UTX/KDM6A 在人多能干细胞神经分化过程中抑制 AP-1 和胶质细胞生成程序


已知 UTX/KDM6A 会相互作用并影响多种不同的染色质修饰剂，以促进开放的染色质环境，从而促进基因激活，但其在发育基因调控中的分子活性仍不清楚。我们报告说，在人类神经干细胞中，UTX 结合与基因表达的促进和抑制相关。这些活性使 UTX 能够调节神经干细胞自我更新、促进神经发生并抑制胶质细胞生成。在神经干细胞中，UTX 对组蛋白 H3 赖氨酸 27 和赖氨酸 4 甲基化的影响较小，但主要影响组蛋白 H3 赖氨酸 27 乙酰化和染色质可及性。此外，UTX 抑制 AP-1 的成分，进而抑制胶质细胞生成程序。我们的研究结果表明，UTX 协调二元基因调控来控制神经干细胞特性和神经发生-胶质细胞发生转换。