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

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 o...

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Bibliographic Details
Published in:Biology of reproduction 2018-06, Vol.98 (6), p.846-855
Main Authors: Lei, Jinzhi, Nie, Qing, Chen, Dong-bao
Format: Article
Language:English
Subjects:
Cell division
Deoxyribonucleic acid
developmental
DNA
DNA methylation
Epigenetics
genomic imprinting
Reproductive health
reprogramming
Sperm
transgenerational inheritance
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Summary: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.
ISSN:0006-3363
1529-7268
DOI:10.1093/biolre/ioy050