title: Differential gene body methylation and reduced expression of cell adhesion and neurotransmitter receptor genes in adverse maternal environment.
abstract: Early life adversity, including adverse gestational and postpartum maternal environment, is a contributing factor in the development of autism, attention deficit hyperactivity disorder (ADHD), anxiety and depression but little is known about the underlying molecular mechanism. In a model of gestational maternal adversity that leads to innate anxiety, increased stress reactivity and impaired vocal communication in the offspring, we asked if a specific DNA methylation signature is associated with the emergence of the behavioral phenotype. Genome-wide DNA methylation analyses identified 2.3% of CpGs as differentially methylated (that is, differentially methylated sites, DMSs) by the adverse environment in ventral-hippocampal granule cells, neurons that can be linked to the anxiety phenotype. DMSs were typically clustered and these clusters were preferentially located at gene bodies. Although CpGs are typically either highly methylated or unmethylated, DMSs had an intermediate (20-80%) methylation level that may contribute to their sensitivity to environmental adversity. The adverse maternal environment resulted in either hyper or hypomethylation at DMSs. Clusters of DMSs were enriched in genes that encode cell adhesion molecules and neurotransmitter receptors; some of which were also downregulated, indicating multiple functional deficits at the synapse in adversity. Pharmacological and genetic evidence links many of these genes to anxiety.
authors: Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA. jio2002@med.cornell.edu
authors: J-E
authors: JE
authors: Oh
authors: N
authors: N
authors: Chambwe
authors: S
authors: S
authors: Klein
authors: J
authors: J
authors: Gal
authors: S
authors: S
authors: Andrews
authors: G
authors: G
authors: Gleason
authors: R
authors: R
authors: Shaknovich
authors: A
authors: A
authors: Melnick
authors: F
authors: F
authors: Campagne
authors: M
authors: M
authors: Toth
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D018891:Dentate Gyrus / Q000378:metabolism*; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics*; D014828:Vocalization, Animal / Q000502:physiology
chemical_list: D044282:Receptor, Serotonin, 5-HT1A