Methylation of the tyrosine hydroxylase gene is dysregulated by cocaine dependence in the human striatum.
| Title | Methylation of the tyrosine hydroxylase gene is dysregulated by cocaine dependence in the human striatum. |
| Publication Type | Journal Article |
| Year of Publication | 2021 |
| Authors | Vaillancourt K, Chen GG, Fiori L, Maussion G, Yerko V, Théroux J-F, Ernst C, Labonte B, Calipari E, Nestler EJ, Nagy C, Mechawar N, Mash DC, Turecki G |
| Journal | iScience |
| Volume | 24 |
| Issue | 10 |
| Pagination | 103169 |
| Date Published | 2021 Oct 22 |
| ISSN | 2589-0042 |
| Abstract | Cocaine dependence is a chronic, relapsing disorder caused by lasting changes in the brain. Animal studies have identified cocaine-related alterations in striatal DNA methylation; however, it is unclear how methylation is related to cocaine dependence in humans. We generated methylomic profiles of the nucleus accumbens using human postmortem brains from a cohort of individuals with cocaine dependence and healthy controls (n = 25 per group). We found hypermethylation in a cluster of CpGs within the gene body of tyrosine hydroxylase containing a putative binding site for the early growth response 1 (EGR1) transcription factor, which is hypermethylated in the caudate nucleus of cocaine-dependent individuals. We replicated this finding and found it to be specific to striatal neuronal nuclei. Furthermore, this locus demonstrates enhancer activity which is attenuated by methylation and enhanced by EGR1 overexpression. These results suggest that cocaine dependence alters the epigenetic regulation of dopaminergic signaling genes. |
| DOI | 10.1016/j.isci.2021.103169 |
| Alternate Journal | iScience |
| PubMed ID | 34693223 |
| PubMed Central ID | PMC8517202 |
| Grant List | P01 DA047233 / DA / NIDA NIH HHS / United States R01 DA007359 / DA / NIDA NIH HHS / United States |