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28 February 2018 A single-cell epigenetic model for paternal psychological stress-induced transgenerational reprogramming in offspring
Jinzhi Lei, Qing Nie, Dong-bao Chen
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Abstract

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.

Summary Sentence

A positive feedback to DNA methylation in the promoter region of an imprinted gene is a possible mechanism to mediate the parental psychological stress reprogramming in offspring.

© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Jinzhi Lei, Qing Nie, and Dong-bao Chen "A single-cell epigenetic model for paternal psychological stress-induced transgenerational reprogramming in offspring ," Biology of Reproduction 98(6), 846-855, (28 February 2018). https://doi.org/10.1093/biolre/ioy050
Received: 18 October 2017; Accepted: 25 February 2018; Published: 28 February 2018
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