title: Proteasome regulates transcription-favoring histone methylation, acetylation and ubiquitination in long-term synaptic plasticity.
abstract: Histone modifications, such as lysine methylation, acetylation and ubiquitination, are epigenetic tags that shape the chromatin landscape and regulate transcription required for synaptic plasticity and memory. Here, we show that transcription-promoting histone H3 trimethylated at lysine 4 (H3K4me3), histone H3 acetylated at lysine 9 and 14 (H3K9/14ac), and histone H2B monoubiquitinated at lysine 120 (H2BK120ub) are enhanced after the induction of long-lasting chemically-induced long-term potentiation (cLTP) in the murine hippocampus. While H3K4me3 and H3K9/14ac were transiently upregulated, H2BK120ub levels oscillated after cLTP induction. In addition, we present results showing that blocking the proteasome, a molecular complex specialized for targeted protein degradation, inhibited the upregulation of these epigenetic tags after cLTP. Thus, our study provides the initial steps toward understanding the role of the proteasome in regulating histone modifications critical for synaptic plasticity.
authors: Department of Neurobiology and Anatomy, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
authors: Svitlana V
authors: SV
authors: Bach
authors: Department of Neurobiology and Anatomy, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
authors: P Ryan
authors: PR
authors: Tacon
authors: Department of Neurobiology and Anatomy, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
authors: James W
authors: JW
authors: Morgan
authors: Department of Neurobiology and Anatomy, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Electronic address: ahegde@wakehealth.edu.
authors: Ashok N
authors: AN
authors: Hegde
mesh_terms: D000107:Acetylation; D000818:Animals; D006657:Histones / Q000378:metabolism*; D017774:Long-Term Potentiation; D008297:Male; D008745:Methylation; D051379:Mice; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D014158:Transcription, Genetic; D054875:Ubiquitination; D015854:Up-Regulation
chemical_list: D006657:Histones; D046988:Proteasome Endopeptidase Complex
keywords: Epigenetic modification; Long-term potentiation; Proteolysis; Transcription; Ubiquitin