Institute of Animal Science, Agricultural Research Organization, The Volcani Center, Bet Dagan 50250, Israel.
Dev Neurobiol. 2010 Feb;70(2):100-13. doi: 10.1002/dneu.20763.
Thermal control set point is regulated by thermosensitive neurons of the preoptic anterior hypothalamus (PO/AH) and completes its development during postnatal critical sensory period. External stimuli, like increase in environmental temperature, influence the neuronal protein repertoire and, ultimately, cell properties via activation or silencing of gene transcription, both of which are regulated by the "histone code.''" Here, we demonstrated an increase in global histone H3 lysine 9 (H3K9) acetylation as well as H3K9 dimethylation in chick PO/AH during heat conditioning at the critical period of sensory development. In contrast to the global profile of H3K9 modifications, acetylation and dimethylation patterns of H3K9 at the promoter of the catalytic subunit of eukaryotic translation initiation factor 2B (Eif2b5) were opposite to each other. During heat conditioning, there was an increase in H3K9 acetylation at the Eif2b5 promoter, simultaneously with decrease in H3K9 dimethylation. These alterations coincided with Eif2b5 mRNA induction. Moreover, exposure to excessive heat during the critical period resulted in long-term effect on both H3K9 tagging at the Eif2b5 promoter and Eif2b5 mRNA expression. These data suggest a role for dynamic H3K9 post-translational modifications in global translation regulation during the thermal control establishment.
体温调定点由视前前下丘脑(PO/AH)的热敏神经元调节,并在出生后关键感觉期完成其发育。外部刺激,如环境温度升高,通过激活或沉默基因转录来影响神经元蛋白组成,最终影响细胞特性,而这两者均受“组蛋白密码”调控。在这里,我们发现在感觉发育关键期的热适应过程中,小鸡 PO/AH 中的组蛋白 H3 赖氨酸 9(H3K9)乙酰化和 H3K9 二甲基化整体水平增加。与 H3K9 修饰的整体模式相反,真核翻译起始因子 2B(Eif2b5)催化亚基启动子处的 H3K9 乙酰化和二甲基化模式彼此相反。在热适应过程中,Eif2b5 启动子处的 H3K9 乙酰化增加,同时 H3K9 二甲基化减少。这些变化与 Eif2b5 mRNA 的诱导相一致。此外,在关键期暴露于过热环境会对 Eif2b5 启动子处的 H3K9 标记和 Eif2b5 mRNA 表达产生长期影响。这些数据表明,动态 H3K9 翻译后修饰在体温控制建立过程中的整体翻译调控中起作用。