Widespread promoter methylation of synaptic plasticity genes in long-term potentiation in the adult brain in vivo.

Abstract:

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.

journal_name

BMC Genomics

journal_title

BMC genomics

authors

Maag JL,Kaczorowski DC,Panja D,Peters TJ,Bramham CR,Wibrand K,Dinger ME

doi

10.1186/s12864-017-3621-x

subject

Has Abstract

pub_date

2017-03-23 00:00:00

pages

250

issue

1

issn

1471-2164

pii

10.1186/s12864-017-3621-x

journal_volume

18

pub_type

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