Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-21348-4
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Funding
- Israel Academy of Sciences [734/13, 1228/18, 282/16, 184/16]
- ISF-NSFC [2013/14, 2555/16]
- Israel Cancer Research Foundation [211410, 210910]
- Binational Science Foundation [2100289]
- Emanuel Rubin Chair in Medical Sciences
- Israel Center of Excellence Program [1796/12]
- German Israeli Foundation [1424]
- Rosetrees Foundation
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A highly regulated epigenetic mark, AS-RT, established during early embryogenesis, has been found to facilitate the programming of mono-allelic choice throughout development.
Stochastic asynchronous replication timing (AS-RT) is a phenomenon in which the time of replication of each allele is different, and the identity of the early allele varies between cells. By taking advantage of stable clonal pre-B cell populations derived from C57BL6/Castaneous mice, we have mapped the genome-wide AS-RT loci, independently of genetic differences. These regions are characterized by differential chromatin accessibility, mono-allelic expression and include new gene families involved in specifying cell identity. By combining population level mapping with single cell FISH, our data reveal the existence of a novel regulatory program that coordinates a fixed relationship between AS-RT regions on any given chromosome, with some loci set to replicate in a parallel and others set in the anti-parallel orientation. Our results show that AS-RT is a highly regulated epigenetic mark established during early embryogenesis that may be used for facilitating the programming of mono-allelic choice throughout development. Most regions of the mammalian genome replicate both alleles in a synchronous manner, but some loci have been found to replicate asynchronously and the time of replication of each allele is different. Here the authors, by employing clonal mouse cells from a hybrid strain chart replication timing over the entire genome, using polymorphisms to distinguish between the paternal and maternal alleles.
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