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核外围对H3K9me2标记的基因和转位子进行抑制,以塑造细胞命运

Harold Marin¹, Eric Simental^2,3, Charlie Allen¹

¹Cardiovascular Research Institute, University of California, San Francisco, CA, USA.

bioRxiv : the preprint server for biology

|July 19, 2024

概括

核外围对于异色素蛋白的功能至关重要. 移除核层会破坏异色染色体的定位,损害基因沉默和细胞分化.

科学领域:

细胞生物学细胞生物学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
发展生物学发展生物学

背景情况:

异色染色素,标记为素H3氨酸9二甲基化 (H3K9me2),通常局部化到核外围在metazoans.
这种空间定位对异色色素活性的功能影响在很大程度上仍未定义.

研究的目的:

研究核外围在调节异色素蛋白功能的作用及其对细胞命运的影响.
确定H3K9me2异色素的空间定位是否对基因沉默和细胞分化至关重要.

主要方法:

小鼠胚胎干细胞 (mESCs) 经过工程设计,缺少三个核层和层B受体 (LBR).
分析异染色体局部化,H3K9me2水平,基因表达和突变mESCs和衍生的表皮质状细胞 (EpiLCs) 的分化潜力.

主要成果:

缺乏膜和LBR的突变mESCs显示异位染色质从核外围脱离.
这些细胞保持了多能性和全球H3K9me2水平,但表现出H3K9me2标记基因和转子体的抑制受损.
突变细胞未能分化为EpiLCs,这一过程依赖于H3K9me2全基因组扩张,分化的EpiLCs无法抑制替代细胞命运标记.

结论:

核外围对于H3K9me2异色素的空间组织,动态调节和抑制功能至关重要.
适当的异染色质定位对于维持原始多能性,促进分化和确保准确的细胞命运决定至关重要.

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