Role of Tet1 and 5-hydroxymethylcytosine in cocaine action (RNA-Seq)

Here we show that Tet1 is down-regulated in mouse nucleus accumbens (NAc), a key brain reward structure, by repeated cocaine administration which enhances behavioral responses to cocaine. Through genome-wide 5hmC profiling, we identified 5hmC changes selectively clustered in both enhancer and coding regions of genes with several annotated neural functions. By coupling with mRNA sequencing, we found cocaine-induced alterations in 5hmC correlate positively with alternative splicing. We also demonstrated that 5hmC alteration at certain genes lasts up to a month after cocaine exposure. Overall design: RNA Nac samples were collected at various time points after 7 daily cocaoine ip administration for 5hmC and transcriptome analysis

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Feng J, Shao N, Szulwach KE, Vialou V, Huynh J, Zhong C, Le T, Ferguson D, Cahill ME, Li Y, Koo JW, Ribeiro E, Labonte B, Laitman BM, Estey D, Stockman V, Kennedy P, Couroussé T, Mensah I, Turecki G, Faull KF, Ming GL, Song H, Fan G, Casaccia P, Shen L, Jin P, Nestler EJ