PDF(Pubmed)
Abstract：
Asymmetric cell divisions (ACDs) generate two daughter cells with identical genetic information but distinct cell fates through epigenetic mechanisms. However, the process of partitioning different epigenetic information into daughter cells remains unclear. Here, we demonstrate that the nucleosome remodeling and deacetylase (NuRD) complex is asymmetrically segregated into the surviving daughter cell rather than the apoptotic one during ACDs in Caenorhabditis elegans. The absence of NuRD triggers apoptosis via the EGL-1-CED-9-CED-4-CED-3 pathway, while an ectopic gain of NuRD enables apoptotic daughter cells to survive. We identify the vacuolar H+-adenosine triphosphatase (V-ATPase) complex as a crucial regulator of NuRD\'s asymmetric segregation. V-ATPase interacts with NuRD and is asymmetrically segregated into the surviving daughter cell. Inhibition of V-ATPase disrupts cytosolic pH asymmetry and NuRD asymmetry. We suggest that asymmetric segregation of V-ATPase may cause distinct acidification levels in the two daughter cells, enabling asymmetric epigenetic inheritance that specifies their respective life-versus-death fates.
摘要：
不对称细胞分裂（ACDs）通过表观遗传机制产生具有相同遗传信息但不同细胞命运的两个子细胞。然而,将不同的表观遗传信息分为子细胞的过程尚不清楚.这里,我们证明，在秀丽隐杆线虫的ACD过程中，核小体重塑和脱乙酰酶（NuRD）复合物不对称地分离到存活的子细胞中，而不是凋亡的子细胞中。NuRD的缺失通过EGL-1-CED-9-CED-4-CED-3通路触发细胞凋亡，而NuRD的异位获得使凋亡的子细胞能够存活。我们确定液泡H-腺苷三磷酸酶（V-ATPase）复合物是NuRD不对称分离的关键调节剂。V-ATP酶与NuRD相互作用，并不对称地分离到存活的子细胞中。抑制V-ATPase破坏细胞溶质pH不对称性和NuRD不对称性。我们建议V-ATPase的不对称分离可能会导致两个子细胞中不同的酸化水平。实现不对称表观遗传，指定他们各自的生与死命运。
