DESCRIPTION:

Genes that have both differential 5-hydroxymethylcytosine (5hmC) levels and alternative splicing patterns in response to cocaine in adult (8-10 week) male C57BL/6J mice. 5hmC levels were measured via 5hmC-seq. Data taken from Supplementary Table 6. Values presented are log2 fold change for 5hmC levels. Data available at GEO with accession number GSE63749.

LABEL:

mouse cocaine alt splice

SCORE TYPE:

Effect

DATE ADDED:

2021-06-24

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Jian Feng, Ningyi Shao, Keith E Szulwach, Vincent Vialou, Jimmy Huynh, Chun Zhong, Thuc Le, Deveroux Ferguson, Michael E Cahill, Yujing Li, Ja Wook Koo, Efrain Ribeiro, Benoit Labonte, Benjamin M Laitman, David Estey, Victoria Stockman, Pamela Kennedy, Thomas Couroussé, Isaac Mensah, Gustavo Turecki, Kym F Faull, Guo-li Ming, Hongjun Song, Guoping Fan, Patrizia Casaccia, Li Shen, Peng Jin, Eric J Nestler

TITLE:

Role of Tet1 and 5-hydroxymethylcytosine in cocaine action.

JOURNAL:

Nature neuroscience Apr 2015, Vol 18, pp. 536-44

ABSTRACT:

Ten-eleven translocation (TET) enzymes mediate the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which is enriched in brain, and its ultimate DNA demethylation. However, the influence of TET and 5hmC on gene transcription in brain remains elusive. We found that ten-eleven translocation protein 1 (TET1) was downregulated in mouse nucleus accumbens (NAc), a key brain reward structure, by repeated cocaine administration, which enhanced behavioral responses to cocaine. We then identified 5hmC induction in putative enhancers and coding regions of genes that have pivotal roles in drug addiction. Such induction of 5hmC, which occurred similarly following TET1 knockdown alone, correlated with increased expression of these genes as well as with their alternative splicing in response to cocaine administration. In addition, 5hmC alterations at certain loci persisted for at least 1 month after cocaine exposure. Together, these reveal a previously unknown epigenetic mechanism of cocaine action and provide new insight into how 5hmC regulates transcription in brain in vivo. PUBMED: 25774451
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