UTX/KDM6A 在人多能干细胞的神经分化过程中抑制 AP-1 和神经发生程序。
UTX/KDM6A suppresses AP-1 and a gliogenesis program during neural differentiation of human pluripotent stem cells.
机构信息
Center for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
出版信息
Epigenetics Chromatin. 2020 Sep 25;13(1):38. doi: 10.1186/s13072-020-00359-3.
BACKGROUND
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.
RESULTS
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.
CONCLUSIONS
Our findings revealed that UTX coordinates dualistic gene regulation to govern neural stem cell properties and neurogenesis-gliogenesis switch.
背景
已知 UTX/KDM6A 可与多种不同的染色质修饰物相互作用并影响它们，以促进开放染色质环境，从而促进基因激活，但它在发育基因调控中的分子活动仍不清楚。
结果
我们报告称，在人类神经干细胞中，UTX 结合与促进和抑制基因表达都有关。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，并抑制神经胶质瘤发生。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，但更主要地影响组蛋白 H3 赖氨酸 27 乙酰化和染色质可及性。此外，UTX 抑制 AP-1 的组成部分，进而抑制神经胶质瘤发生程序。
结论
我们的研究结果表明，UTX 协调二元基因调控，以控制神经干细胞特性和神经发生-神经胶质瘤发生转换。
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