Adolescent binge-pattern alcohol exposure alters genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve male offspring.
Teenage binge drinking is a major health concern in the United States, with 21% of teenagers reporting binge-pattern drinking behavior in the previous 30 days. Recently, our lab showed that alcohol-naïve offspring of rats exposed to alcohol during adolescence exhibited altered gene expression profiles in the hypothalamus, a brain region involved in stress regulation. We employed Enhanced Reduced Representation Bisulfite Sequencing as an unbiased approach to test the hypothesis that parental exposure to binge-pattern alcohol during adolescence alters DNA methylation profiles in their alcohol-naïve offspring. Wistar rats were administered a repeated binge-ethanol exposure paradigm during early (postnatal day (PND) 37-44) and late (PND 67-74) adolescent development. Animals were mated 24 h after the last ethanol dose and subsequent offspring were produced. Analysis of male PND7 offspring revealed that offspring of alcohol-exposed parents exhibited differential DNA methylation patterns in the hypothalamus. The differentially methylated cytosines (DMCs) were distinct between offspring depending on which parent was exposed to ethanol. Moreover, novel DMCs were observed when both parents were exposed to ethanol and many DMCs from single parent ethanol exposure were not recapitulated with dual parent exposure. We also measured mRNA expression of several differentially methylated genes and some, but not all, showed correlative changes in expression. Importantly, methylation was not a direct predictor of expression levels, underscoring the complexity of transcriptional regulation. Overall, we demonstrate that adolescent binge ethanol exposure causes altered genome-wide DNA methylation patterns in the hypothalamus of alcohol-naïve offspring.
Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, IL, USA.
AnnaDorothea
A
Asimes
Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, IL, USA.
Audrey
A
Torcaso
Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, IL, USA.
Elena
E
Pinceti
Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, IL, USA.
Chun K
CK
Kim
Department of Medicine, Loyola University Chicago, Maywood, IL, USA.
Nancy J
NJ
Zeleznik-Le
Department of Cell and Molecular Physiology, Loyola University Chicago, Maywood, IL, USA. Electronic address: tpak@luc.edu.
Toni R
TR
Pak
D000367:Age Factors; D000818:Animals; D063425:Binge Drinking / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation; D040941:Heredity; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D040582:Inheritance Patterns; D008297:Male; D023421:Models, Animal; D010375:Pedigree; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D046468:Sexual Development; D013997:Time Factors; D000066608:Underage Drinking
D012333:RNA, Messenger; D000431:Ethanol
Adolescence; Alcohol; DNA methylation; Epigenetics; Inheritance