Cocaine-related DNA methylation in caudate neurons alters 3D chromatin structure of the IRXA gene cluster.

ABSTRACT: Epigenetic mechanisms, like those involving DNA methylation, are thought to mediate the relationship between chronic cocaine dependence and molecular changes in addiction-related neurocircuitry, but have been understudied in human brain. We initially used reduced representation bisulfite sequencing (RRBS) to generate a methylome-wide profile of cocaine dependence in human post-mortem caudate tissue. We focused on the Iroquois Homeobox A (IRXA) gene cluster, where hypomethylation in exon 3 of IRX2 in neuronal nuclei was associated with cocaine dependence. We replicated this finding in an independent cohort and found similar results in the dorsal striatum from cocaine self-administering mice. Using epigenome editing and 3C assays, we demonstrated a causal relationship between methylation wit

SUBMITTER: Vaillancourt K 

PROVIDER: S-EPMC8039060 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature