TY - JOUR T1 - Sexual dimorphism in epigenomic responses of stem cells to extreme fetal growth JF - bioRxiv DO - 10.1101/008482 SP - 008482 AU - Fabien Delahaye AU - N. Ari Wijetunga AU - Hye J. Heo AU - Jessica N. Tozour AU - Yong Mei Zhao AU - John M. Greally AU - Francine H. Einstein Y1 - 2014/01/01 UR - http://biorxiv.org/content/early/2014/08/27/008482.abstract N2 - Extreme fetal growth is associated with increased susceptibility to a range of adult diseases through an unknown mechanism of cellular memory. We tested whether heritable epigenetic processes in long-lived CD34+ hematopoietic stem/progenitor cells (HSPCs) showed evidence for re-programming associated with the extremes of fetal growth. Here we show that both fetal growth restriction and over-growth are associated with global shifts towards DNA hypermethylation, targeting cis-regulatory elements in proximity to genes involved in glucose homeostasis and stem cell function. A sexually dimorphic response was found, intrauterine growth restriction (IUGR) associated with substantially greater epigenetic dysregulation in males but large for gestational age (LGA) growth affecting females predominantly. The findings are consistent with extreme fetal growth interacting with variable fetal susceptibility to influence cellular aging and metabolic characteristics through epigenetic mechanisms, potentially generating biomarkers that could identify infants at higher risk for chronic disease later in life. ER -