title: Alcohol exposure decreases CREB binding protein expression and histone acetylation in the developing cerebellum.
abstract: BACKGROUND
  Fetal alcohol exposure affects 1 in 100 children making it the leading cause of mental retardation in the US. It has long been known that alcohol affects cerebellum development and function. However, the underlying molecular mechanism is unclear.
  
  
  RESULTS
  We demonstrate that CREB binding protein (CBP) is widely expressed in granule and Purkinje neurons of the developing cerebellar cortex of naïve rats. We also show that exposure to ethanol during the 3(rd) trimester-equivalent of human pregnancy reduces CBP levels. CBP is a histone acetyltransferase, a component of the epigenetic mechanism controlling neuronal gene expression. We further demonstrate that the acetylation of both histone H3 and H4 is reduced in the cerebellum of ethanol-treated rats.
  
  
  CONCLUSIONS
  These findings indicate that ethanol exposure decreases the expression and function of CBP in the developing cerebellum. This effect of ethanol may be responsible for the motor coordination deficits that characterize fetal alcohol spectrum disorders.
authors.affiliation: Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America.
authors.forename: Weixiang
authors.initials: W
authors.lastname: Guo
authors.forename: Erin L
authors.initials: EL
authors.lastname: Crossey
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Stefano
authors.initials: S
authors.lastname: Zucca
authors.forename: Olivia L
authors.initials: OL
authors.lastname: George
authors.forename: C Fernando
authors.initials: CF
authors.lastname: Valenzuela
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D050882:CREB-Binding Protein / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006657:Histones / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D051381:Rats
chemical_list: D006657:Histones; D000431:Ethanol; D050882:CREB-Binding Protein