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Sequences sufficient for programming imprinted germline dna methylation defined

Title
Sequences sufficient for programming imprinted germline dna methylation defined
Authors
Park Y.J.Herman H.Gao Y.Lindroth A.M.Hu B.Y.Murphy P.J.Putnam J.R.Soloway P.D.
Ewha Authors
박윤정
SCOPUS Author ID
박윤정scopus
Issue Date
2012
Journal Title
PLoS ONE
ISSN
1932-6203JCR Link
Citation
vol. 7, no. 3
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Epigenetic marks are fundamental to normal development, but little is known about signals that dictate their placement. Insights have been provided by studies of imprinted loci in mammals, where monoallelic expression is epigenetically controlled. Imprinted expression is regulated by DNA methylation programmed during gametogenesis in a sex-specific manner and maintained after fertilization. At Rasgrf1 in mouse, paternal-specific DNA methylation on a differential methylation domain (DMD) requires downstream tandem repeats. The DMD and repeats constitute a binary switch regulating paternal-specific expression. Here, we define sequences sufficient for imprinted methylation using two transgenic mouse lines: One carries the entire Rasgrf1 cluster (RC); the second carries only the DMD and repeats (DR) from Rasgrf1. The RC transgene recapitulated all aspects of imprinting seen at the endogenous locus. DR underwent proper DNA methylation establishment in sperm and erasure in oocytes, indicating the DMD and repeats are sufficient to program imprinted DNA methylation in germlines. Both transgenes produce a DMD-spanning pit-RNA, previously shown to be necessary for imprinted DNA methylation at the endogenous locus. We show that when pit-RNA expression is controlled by the repeats, it regulates DNA methylation in cis only and not in trans. Interestingly, pedigree history dictated whether established DR methylation patterns were maintained after fertilization. When DR was paternally transmitted followed by maternal transmission, the unmethylated state that was properly established in the female germlines could not be maintained. This provides a model for transgenerational epigenetic inheritance in mice. © 2012 Park et al.
DOI
10.1371/journal.pone.0033024
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신산업융합대학 > 식품영양학과 > Journal papers
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