DNMT1 通过抑制 p53 来维持胰腺器官发生过程中的祖细胞存活。
DNMT1 represses p53 to maintain progenitor cell survival during pancreatic organogenesis.
机构信息
Department of Medicine, University of California at Los Angeles, Los Angeles, California 90024, USA.
出版信息
Genes Dev. 2013 Feb 15;27(4):372-7. doi: 10.1101/gad.207001.112.
Abstract
In the developing pancreas, self-renewal of progenitors and patterning of cell fates are coordinated to ensure the correct size and cellular makeup of the organ. How this coordination is achieved, however, is not clear. We report that deletion of DNA methyltransferase 1 (Dnmt1) in pancreatic progenitors results in agenesis of the pancreas due to apoptosis of progenitor cells. We show that DNMT1 is bound to the p53 regulatory region and that loss of Dnmt1 results in derepression of the p53 locus. Haploinsufficiency of p53 rescues progenitor cell survival and cellular makeup of the Dnmt1-deleted pancreas.
摘要
在发育中的胰腺中，祖细胞的自我更新和细胞命运的模式形成是协调一致的，以确保器官的正确大小和细胞组成。然而，这种协调是如何实现的尚不清楚。我们报告称，祖细胞中 DNA 甲基转移酶 1 (Dnmt1) 的缺失会导致胰腺发育不全，这是由于祖细胞凋亡所致。我们表明，DNMT1 与 p53 调控区结合，并且 Dnmt1 的缺失导致 p53 基因座的去抑制。p53 的单倍不足挽救了 Dnmt1 缺失的祖细胞的存活和细胞组成。
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