Sex differences in gene expression and proliferation are dependent on the epigenetic modifier HP1?
Sex differences in gene expression and proliferation are dependent on the epigenetic modifier HP1?
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基因表达和增殖的性别差异取决于表观遗传修饰剂 HP1？
DOI：
10.1101/563940
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Law P
中科院分区：
文献类型：
--
作者：
Law P
早期胚胎生长速度的性别差异已在多种哺乳动物中得到承认，并被归因于性染色体互补效应，因为它们发生在显性分化之前。我们之前发现，性染色体互补，而不是性激素调节异染色质介导的转基因和常染色体基因表达的沉默。在这里，研究了增殖过程中的性别二型性。我们证实，男性胚胎成纤维细胞比女性成纤维细胞增殖更快，并表明这种增殖优势完全依赖于异染色质蛋白1伽马(Hp1γ)。为了确定Hp1γ的这种性别调节作用是否是一种更普遍的现象，我们对来自男性和女性的MEF进行了RNA测序，无论有没有Hp1γ。值得注意的是，Hp1γ被发现对调节几乎所有性二态常染色体基因的表达至关重要，因为男性Hp1γ基因的缺失消除了常染色体基因表达的性别差异。确定一个关键的表观遗传修饰物作为确定男性和女性基因表达差异的核心，对于理解疾病中的生理性别差异和性别偏见具有重要意义。
Sex differences in growth rate in very early embryos have been recognized in a variety of mammals and attributed to sex-chromosome complement effects as they occur before overt sexual differentiation. We previously found that sex-chromosome complement, rather than sex hormones regulates heterochromatin-mediated silencing of a transgene and autosomal gene expression in mice. Here, sex dimorphism in proliferation was investigated. We confirm that male embryonic fibroblasts proliferate faster than female fibroblasts and show that this proliferation advantage is completely dependent upon heterochromatin protein 1 gamma (HP1γ). To determine whether this sex-regulatory effect of HP1γ was a more general phenomenon, we performed RNA sequencing on MEFs derived from males and females, with or without HP1γ. Strikingly, HP1γ was found to be crucial for regulating nearly all sexually dimorphic autosomal gene expression because deletion of the HP1γ gene in males abolished sex differences in autosomal gene expression. The identification of a key epigenetic modifier as central in defining gene expression differences between males and females has important implications for understanding physiological sex differences and sex bias in disease.