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Publication : A single-cell epigenetic model for paternal psychological stress-induced transgenerational reprogramming in offspring.

First Author  Lei J Year  2018
Journal  Biol Reprod Volume  98
Issue  6 Pages  846-855
PubMed ID  29506130 Mgi Jnum  J:262518
Mgi Id  MGI:6160501 Doi  10.1093/biolre/ioy050
Citation  Lei J, et al. (2018) A single-cell epigenetic model for paternal psychological stress-induced transgenerational reprogramming in offspring. Biol Reprod 98(6):846-855
abstractText  Experimental evidence shows that parental psychological stress affects the long-term health of offspring in an inheritable fashion. Although epigenetic mechanisms, including DNA methylation, miRNA, and histone modifications, are involved in transgenerational programming, the underlining mechanisms of transgenerational inheritance remain unsolved. Here, we present a single-cell-based computational model for transgenerational inheritance for investigating the long-term dynamics of phenotype changes in response to parental stress. The model is based on a recent study that has identified the imprinted sperm gene Sfmbt2 as a key target, and incorporates crosstalks among drastically different time scales in mammalian development, including DNA methylation, transcription, cell division, and population dynamics. Computational analysis of the model suggests a positive feedback to DNA methylation in the promoter region of sperm Sfmbt2 gene that provides a possible mechanism to mediate the parental psychological stress reprogramming in offspring. This approach provides a modeling framework for the understanding of the roles that epigenetics play in transgenerational inheritance.
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