PMID- 28335720 OWN - NLM STAT- MEDLINE DCOM- 20171225 LR - 20181113 IS - 1471-2164 (Electronic) IS - 1471-2164 (Linking) VI - 18 IP - 1 DP - 2017 Mar 23 TI - Widespread promoter methylation of synaptic plasticity genes in long-term potentiation in the adult brain in vivo. PG - 250 LID - 10.1186/s12864-017-3621-x [doi] LID - 250 AB - BACKGROUND: DNA methylation is a key modulator of gene expression in mammalian development and cellular differentiation, including neurons. To date, the role of DNA modifications in long-term potentiation (LTP) has not been explored. RESULTS: To investigate the occurrence of DNA methylation changes in LTP, we undertook the first detailed study to describe the methylation status of all known LTP-associated genes during LTP induction in the dentate gyrus of live rats. Using a methylated DNA immunoprecipitation (MeDIP)-array, together with previously published matched RNA-seq and public histone modification data, we discover widespread changes in methylation status of LTP-genes. We further show that the expression of many LTP-genes is correlated with their methylation status. We show that these correlated genes are enriched for RNA-processing, active histone marks, and specific transcription factors. These data reveal that the synaptic activity-evoked methylation changes correlates with pre-existing activation of the chromatin landscape. Finally, we show that methylation of Brain-derived neurotrophic factor (Bdnf) CpG-islands correlates with isoform switching from transcripts containing exon IV to exon I. CONCLUSIONS: Together, these data provide the first evidence of widespread regulation of methylation status in LTP-associated genes. FAU - Maag, Jesper L V AU - Maag JL AD - Division of Genomics and Epigenetics, Garvan Institute of Medical Research, Sydney, Australia. AD - St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, 370 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia. FAU - Kaczorowski, Dominik C AU - Kaczorowski DC AD - Division of Genomics and Epigenetics, Garvan Institute of Medical Research, Sydney, Australia. FAU - Panja, Debabrata AU - Panja D AD - Department of Biomedicine and K.G. Jebsen Centre for Neuropsychiatric Disorders, University of Bergen, Bergen, Norway. FAU - Peters, Timothy J AU - Peters TJ AD - Division of Genomics and Epigenetics, Garvan Institute of Medical Research, Sydney, Australia. FAU - Bramham, Clive R AU - Bramham CR AD - Department of Biomedicine and K.G. Jebsen Centre for Neuropsychiatric Disorders, University of Bergen, Bergen, Norway. FAU - Wibrand, Karin AU - Wibrand K AD - Department of Biomedicine and K.G. Jebsen Centre for Neuropsychiatric Disorders, University of Bergen, Bergen, Norway. FAU - Dinger, Marcel E AU - Dinger ME AD - Division of Genomics and Epigenetics, Garvan Institute of Medical Research, Sydney, Australia. m.dinger@garvan.org.au. AD - St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, 370 Victoria Street, Darlinghurst, Sydney, NSW, 2010, Australia. m.dinger@garvan.org.au. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170323 PL - England TA - BMC Genomics JT - BMC genomics JID - 100965258 RN - 0 (Chromatin) RN - 0 (Histones) SB - IM MH - Adult MH - Brain/metabolism/*physiology MH - Chromatin/metabolism MH - CpG Islands/genetics MH - *DNA Methylation MH - Gene Expression Regulation MH - Genetic Loci/genetics MH - Histones/metabolism MH - Humans MH - Long-Term Potentiation/*genetics MH - Memory/physiology MH - Neuronal Plasticity/*genetics MH - Oligonucleotide Array Sequence Analysis MH - Promoter Regions, Genetic/*genetics PMC - PMC5364592 OTO - NOTNLM OT - DNA-methylation OT - Epigenetics OT - LTP OT - Long-term potentiation OT - MeDIP OT - Neuroepigenetics OT - Synaptic plasticity EDAT- 2017/03/25 06:00 MHDA- 2017/12/26 06:00 PMCR- 2017/03/23 CRDT- 2017/03/25 06:00 PHST- 2016/09/13 00:00 [received] PHST- 2017/03/11 00:00 [accepted] PHST- 2017/03/25 06:00 [entrez] PHST- 2017/03/25 06:00 [pubmed] PHST- 2017/12/26 06:00 [medline] PHST- 2017/03/23 00:00 [pmc-release] AID - 10.1186/s12864-017-3621-x [pii] AID - 3621 [pii] AID - 10.1186/s12864-017-3621-x [doi] PST - epublish SO - BMC Genomics. 2017 Mar 23;18(1):250. doi: 10.1186/s12864-017-3621-x.