Department of Developmental Biology and Cancer Research, Hebrew University Medical School, Jerusalem, Israel.
The Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University-Hadassah, Jerusalem, Israel.
Nat Struct Mol Biol. 2017 Dec;24(12):1132-1138. doi: 10.1038/nsmb.3503. Epub 2017 Nov 13.
Many regions of the genome replicate asynchronously and are expressed monoallelically. It is thought that asynchronous replication may be involved in choosing one allele over the other, but little is known about how these patterns are established during development. We show that, unlike somatic cells, which replicate in a clonal manner, embryonic and adult stem cells are programmed to undergo switching, such that daughter cells with an early-replicating paternal allele are derived from mother cells that have a late-replicating paternal allele. Furthermore, using ground-state embryonic stem (ES) cells, we demonstrate that in the initial transition to asynchronous replication, it is always the paternal allele that is chosen to replicate early, suggesting that primary allelic choice is directed by preset gametic DNA markers. Taken together, these studies help define a basic general strategy for establishing allelic discrimination and generating allelic diversity throughout the organism.
基因组的许多区域都以不同步的方式进行复制，并单等位基因表达。人们认为，异步复制可能参与了在两个等位基因之间做出选择，但对于这些模式在发育过程中是如何建立的，我们知之甚少。我们表明，与以克隆方式复制的体细胞不同，胚胎和成体干细胞被编程为进行切换，使得具有早期复制的父等位基因的子细胞源自具有晚期复制的父等位基因的母细胞。此外，使用原始态胚胎干细胞（ES 细胞），我们证明在向异步复制的初始转变中，总是选择父等位基因进行早期复制，这表明主要等位基因选择是由配子 DNA 标记预设指导的。总之，这些研究有助于定义一种基本的通用策略，用于在整个生物体中建立等位基因鉴别和产生等位基因多样性。
