Cortical DNA methylation maintains remote memory.
A behavioral memory's lifetime represents multiple molecular lifetimes, suggesting the necessity for a self-perpetuating signal. One candidate is DNA methylation, a transcriptional repression mechanism that maintains cellular memory throughout development. We found that persistent, gene-specific cortical hypermethylation was induced in rats by a single, hippocampus-dependent associative learning experience and pharmacologic inhibition of methylation 1 month after learning disrupted remote memory. We propose that the adult brain utilizes DNA methylation to preserve long-lasting memories.
Miller
Courtney A
CA
Department of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA. cmiller@scripps.edu
Gavin
Cristin F
CF
White
Jason A
JA
Parrish
R Ryley
RR
Honasoge
Avinash
A
Yancey
Christopher R
CR
Rivera
Ivonne M
IM
Rubio
María D
MD
Rumbaugh
Gavin
G
Sweatt
J David
JD
D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D001483:Base Sequence; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D004597:Electroshock; D005239:Fear; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008969:Molecular Sequence Data; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013997:Time Factors
D051766:Early Growth Response Protein 1; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D019703:Calcineurin