title: Epigenetic stability in the adult mouse cortex under conditions of pharmacologically induced histone acetylation.
abstract: Histone acetylation is considered a major epigenetic process that affects brain development and synaptic plasticity, as well as learning and memory. The transcriptional effectors and morphological changes responsible for plasticity as a result of long-term modifications to histone acetylation are not fully understood. To this end, we pharmacologically inhibited histone deacetylation using Trichostatin A in adult (6-month-old) mice and found significant increases in the levels of the acetylated histone marks H3Lys9, H3Lys14 and H4Lys12. High-resolution transcriptome analysis of diverse brain regions uncovered few differences in gene expression between treated and control animals, none of which were plasticity related. Instead, after increased histone acetylation, we detected a large number of novel transcriptionally active regions, which correspond to long non-coding RNAs (lncRNAs). We also surprisingly found no significant changes in dendritic spine plasticity in layers 1 and 2/3 of the visual cortex using long-term in vivo two-photon imaging. Our results indicate that chronic pharmacologically induced histone acetylation can be decoupled from gene expression and instead, may potentially exert a post-transcriptional effect through the differential production of lncRNAs.
authors.affiliation: Department of Psychology, Yale University, New Haven, CT, 06520, USA. jamie.benoit@yale.edu.|Department of Brain and Cognitive Sciences, Picower Institute of Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. jamie.benoit@yale.edu.
authors.forename: Jamie
authors.initials: J
authors.lastname: Benoit
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, New Haven, CT, 06520, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Ayoub
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, New Haven, CT, 06520, USA.|Kavli Institute for Neuroscience Yale University, New Haven, CT, 06520, USA.
authors.forename: Pasko
authors.initials: P
authors.lastname: Rakic
mesh_terms: D000107:Acetylation; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000502:physiology*; D049229:Dendritic Spines / Q000502:physiology; D044127:Epigenesis, Genetic; D005625:Frontal Lobe / Q000378:metabolism / Q000502:physiology; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D006657:Histones / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity; D009778:Occipital Lobe / Q000378:metabolism / Q000502:physiology; D009830:Olfactory Bulb / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D006657:Histones; D012333:RNA, Messenger
keywords: Epigenetics; Histone acetylation; RNA-seq; Synaptic plasticity