Mammalian Development Laboratory, Institute of Medical Biology, Singapore.
Development. 2013 Feb;140(4):853-60. doi: 10.1242/dev.086611. Epub 2013 Jan 14.
Cellular differentiation during embryogenesis involves complex gene regulation to enable the activation and repression of genes. Here, we show that mesodermal competence is inhibited in Xenopus embryos depleted of histones H3 and H3.3, which fail to respond to Nodal/Activin signaling and exhibit concomitant loss of mesodermal gene expression. We find that transcriptional activation in gastrula embryos does not correlate with promoter deposition of H3.3. Instead, gastrulation defects in H3.3/H3-deficient embryos are partially rescued with concurrent depletion of the linker histone H1A. In addition, we show that linker histone H1-induced premature loss of mesodermal competence in animal cap explants can be abrogated with the overexpression of nucleosomal H3.3/H3. Our findings establish a chromatin-mediated regulatory mechanism in which a threshold level of H3 is required to prevent H1-induced gene repression, and thus facilitate mesodermal differentiation in response to inductive signaling.
胚胎发生过程中的细胞分化涉及复杂的基因调控，以激活和抑制基因。在这里，我们表明，缺乏组蛋白 H3 和 H3.3 的非洲爪蟾胚胎中的中胚层能力受到抑制，这些胚胎无法对 Nodal/Activin 信号做出反应，并表现出中胚层基因表达的同时丧失。我们发现，原肠胚胚胎中的转录激活与 H3.3 的启动子沉积不相关。相反，H3.3/H3 缺陷胚胎的原肠胚缺陷部分通过同时耗尽连接组蛋白 H1A 得到挽救。此外，我们表明，在动物帽外植体中，连接组蛋白 H1 诱导的中胚层能力过早丧失可以通过核小体 H3.3/H3 的过表达来消除。我们的研究结果建立了一个染色质介导的调控机制，其中 H3 的阈值水平是防止 H1 诱导的基因抑制所必需的，从而促进对诱导信号的中胚层分化。
