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Novel effects of chromosome Y on cardiac regulation, chromatin remodeling, and neonatal programming in male mice

Item Type:Article
Title:Novel effects of chromosome Y on cardiac regulation, chromatin remodeling, and neonatal programming in male mice
Creators Name:Praktiknjo, S.D. and Llamas, B. and Scott-Boyer, M.P. and Picard, S. and Robert, F. and Langlais, D. and Haibe-Kains, B. and Faubert, D. and Silversides, D.W. and Deschepper, C.F.
Abstract:Little is known about the functions of chromosome Y (chrY) genes beyond their effects on sex and reproduction. In hearts, postpubertal testosterone affects the size of cells and the expression of genes differently in male C57BL/6J than in their C57.Y(A) counterparts, where the original chrY has been substituted with that from A/J mice. We further compared the 2 strains to better understand how chrY polymorphisms may affect cardiac properties, the latter being sexually dimorphic but unrelated to sex and reproduction. Genomic regions showing occupancy with androgen receptors (ARs) were identified in adult male hearts from both strains by chromatin immunoprecipitation. AR chromatin immunoprecipitation peaks (showing significant enrichment for consensus AR binding sites) were mostly strain specific. Measurements of anogenital distances in male pups showed that the biologic effects of perinatal androgens were greater in C57BL/6J than in C57.Y(A). Although perinatal endocrine manipulations showed that these differences contributed to the strain-specific differences in the response of adult cardiac cells to testosterone, the amounts of androgens produced by fetal testes were not different in each strain. Nonetheless, chrY polymorphisms associated in newborn pups' hearts with strain-specific differences in genomic regions showing either AR occupancy, accessible chromatin sites, or trimethylation of histone H3 Lysine 4 marks, as well as with differential expression of 2 chrY-encoded histone demethylases. In conclusion, the effects of chrY on adult cardiac phenotypes appeared to result from an interaction of this chromosome with the organizational programming effects exerted by the neonatal testosterone surge and show several characteristics of being mediated by an epigenetic remodeling of chromatin.
Keywords:Androgens, Chromatin Assembly and Disassembly, Chromatin Immunoprecipitation, Gene Expression Regulation, Genetic Polymorphism, Inbred Strains Mice, Myocardium, Newborn Animals, Y Chromosome, Animals, Mice
Publisher:Endocrine Society
Page Range:4746-4756
Date:1 December 2013
Official Publication:https://doi.org/10.1210/en.2013-1699
PubMed:View item in PubMed

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