在人体组织中X染色体失活的景观
Taru Tukiainen1,2, Alexandra-Chloé Villani2,3, Angela Yen2,4
1Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Nature
|October 13, 2017
概括
在人类中,X染色体不活化 (XCI) 是不完整的,许多基因在不活跃的X染色体上逃脱沉默. 这项研究揭示了跨组织的XCI模式,表明它影响了基因表达和表型多样性.
科学领域:
- 遗传学
- 表观遗传学
- 哺乳动物生物学
背景情况:
- 在哺乳动物中,X染色体不活化 (XCI) 会使两性基因剂量相等.
- 人类XCI是不完整的,一些基因在活跃的 (Xa) 和不活跃的 (Xi) X染色体上脱离不活化.
- 组织特异性和XCI逃逸的个体变异性及其表型后果尚不清楚.
研究的目的:
- 在人类组织和细胞中系统地调查XCI模式.
- 识别脱离XCI的基因并量化不完整XCI的程度.
- 调查XCI逃逸与性别偏差基因表达之间的联系.
主要方法:
- 在29个组织中对GTEx (v6p) 的5500多个转录组进行了综合分析.
- 包含940个单细胞转录组和基因组序列数据.
- 从活跃和不活跃的X染色体中对XCI模式和基因表达的系统调查.
主要成果:
- 在人类组织中,XCI模式在很大程度上是统一的,但在个体和细胞水平上表现出异质性.
- 至少23%的X染色体基因表现出不完整的XCI,其中7个被确定为始终逃脱不活化.
- 脱离XCI导致性别偏差的基因表达,有助于表型多样性.
结论:
- 不完整的XCI是人类遗传学的重要特征,
- 这项研究提供了人体组织中XCI的综合目录,突出了其变异性.
- 不完整的XCI有助于基因表达和潜在的表型特征的性别差异.
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