Poster 13
Presenter: Samantha Praktiknjo
Wednesday, 3:00 – 5:00pm
S.D. Praktiknjo, B. Llamas, M.P. Scott-Boyer, S. Picard and C.F. Deschepper Institut de recherches cliniques de Montréal (IRCM), Montreal (QC) Canada
Little is known about the functions of chromosome Y (chrY) genes beyond their effects on sex and reproduction. We compared C57BL/6J mice to consomic C57.YA counterparts where chrY originates from A/J. In adult hearts, testosterone affected the size of cardiomyocytes in C57BL/6J, but not in C57.YA. In neonatal pups, anogenital distances showed that testosterone exposure was stronger in C57BL/6J than in C57.YA, but when testosterone was antagonized in fetal C56BL/6J, testosterone no longer affected the size of adult cardiomyocytes. Since the amounts of androgens produced by fetal testes were not different in the two strains, we tested whether strain-specific differences in the programming effect of perinatal testosterone could result from epigenetic differences: we studied the distribution of androgen receptors (AR) in cardiac chromatin by ChIP-Seq, and that of accessible chromatin regions by FAIRE-Seq. Both in neonatal and adult hearts, AR ChIP peaks: 1) were mostly strain-specific; 2) were validated (as they showed significant enrichment for consensus AR binding sites); and 3) contained genes that were most significantly enriched for GO or KEGG terms corresponding to heart development or hypertrophy. In neonatal hearts, we also found (by FAIRE-Seq) strain-specific differences for chromatin in open conformation. Gene expression profiling revealed that two chrY-encoded histone demethylases (Uty and Kdm5d) showed strain-specific expression around birth time. Altogether, the effects of chrY on adult cardiac phenotypes appear to result from an interaction of chrY with the organizational programming effects of perinatal testosterone, and show several characteristics of being mediated by an epigenetic remodeling of chromatin.