RT Journal Article
SR Electronic
T1 The formation of extinction memory requires the accumulation of N6-methyl-2’-deoxyadenosine in DNA
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 059972
DO 10.1101/059972
A1 Xiang Li
A1 Wei Wei
A1 Quan Li
A1 Christophe Magnan
A1 Michael Emami
A1 Luis Wearick da Silva
A1 Thiago W. Viola
A1 Paul Marshall
A1 Rodrigo Grassi-Oliveira
A1 Sarah Nainar
A1 Cathrine Broberg Vågbø
A1 Magnar Bjørås
A1 Pierre F. Baldi
A1 Robert C. Spitale
A1 Timothy William Bredy
YR 2016
UL http://biorxiv.org/content/early/2016/06/20/059972.abstract
AB We have discovered that the recently identified mammalian DNA modification N6-methyl-2-deoxyadenosine (m6dA) drives activity-induced gene expression in the adult brain and is associated with the formation of fear extinction memory in C57/Bl6 mice. In activated primary cortical neurons, m6dA accumulates within the P4 promoter of the gene encoding brain-derived neurotrophic factor (bdnf), which is associated with an active chromatin state, as well as the recruitment of the activating transcription factor Yin-Yang 1 and RNA polymerase II, thereby promoting bdnf exon IV mRNA expression. Lentiviral-mediated knockdown of a potential adenine methyltransferase, N6amt1, blocks the effect of neuronal activation on m6dA and its related chromatin and transcriptional machinery in vitro. These effects are recapitulated in the adult brain, where the extinction learning-induced N6amt1-mediated accumulation of m6dA in the infralimbic prefrontal cortex also enhances the expression of bdnf exon IV and is necessary for the formation of fear extinction memory.