PT  - JOURNAL ARTICLE
AU  - Xiang Li
AU  - Wei Wei
AU  - Quan Lin
AU  - Christophe Magnan
AU  - Michael Emami
AU  - Luis Eduardo Wearick-Silva
AU  - Thiago W. Viola
AU  - Paul Marshall
AU  - Rodrigo Grassi-Oliveira
AU  - Sarah Nainar
AU  - Cathrine Broberg Vågbø
AU  - Magnar Bjørås
AU  - Pierre F. Baldi
AU  - Robert C. Spitale
AU  - Timothy W. Bredy
TI  - Extinction memory requires the accumulation of N6-methyl-2’-deoxyadenosine in DNA
AID  - 10.1101/059972
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 059972
4099  - http://biorxiv.org/content/early/2016/06/22/059972.short
4100  - http://biorxiv.org/content/early/2016/06/22/059972.full
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.