PDF(Pubmed)
Abstract：
Histone post-translational modifications are critical for mediating persistent alterations in gene expression. By combining unbiased proteomics profiling and genome-wide approaches, we uncovered a role for mono-methylation of lysine 27 at histone H3 (H3K27me1) in the enduring effects of stress. Specifically, mice susceptible to early life stress (ELS) or chronic social defeat stress (CSDS) displayed increased H3K27me1 enrichment in the nucleus accumbens (NAc), a key brain-reward region. Stress-induced H3K27me1 accumulation occurred at genes that control neuronal excitability and was mediated by the VEFS domain of SUZ12, a core subunit of the polycomb repressive complex-2, which controls H3K27 methylation patterns. Viral VEFS expression changed the transcriptional profile of the NAc, led to social, emotional, and cognitive abnormalities, and altered excitability and synaptic transmission of NAc D1-medium spiny neurons. Together, we describe a novel function of H3K27me1 in the brain and demonstrate its role as a \"chromatin scar\" that mediates lifelong stress susceptibility.
摘要：
组蛋白翻译后修饰对于介导基因表达的持续改变至关重要。通过结合无偏蛋白质组学分析和全基因组方法，我们发现赖氨酸27在组蛋白H3（H3K27me1）的单甲基化在胁迫的持久效应中的作用。具体来说,对早期生活压力（ELS）或慢性社会失败压力（CSDS）敏感的小鼠在伏隔核（NAc）中显示出增加的H3K27me1富集，一个关键的大脑奖励区域。应激诱导的H3K27me1积累发生在控制神经元兴奋性的基因上，并由SUZ12的VEFS结构域介导，SUZ12是多梳抑制复合物2的核心亚基，控制H3K27甲基化模式。病毒VEFS表达改变了NAc的转录谱，导致社会，情感,和认知异常，NAcD1-中等棘突神经元的兴奋性和突触传递改变。一起,我们描述了H3K27me1在大脑中的新功能，并证明了其作为介导终身压力易感性的“染色质瘢痕”的作用。
