DNA methylation and hydroxymethylation characterize the identity of D1 and D2 striatal projection neurons

Lucile Marion-Poll*, Jean Pierre Roussarie, Lieng Taing, Cloelia Dard-Dascot, Nicolas Servant, Yan Jaszczyszyn, Emmanuelle Jordi, Eskeatnaf Mulugeta, Denis Hervé, Déborah Bourc’his, Paul Greengard, Claude Thermes, Jean Antoine Girault*

*Corresponding author for this work

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Abstract

Neuronal DNA modifications differ from those in other cells, including methylation outside CpG context and abundant 5-hydroxymethylation whose relevance for neuronal identities are unclear. Striatal projection neurons expressing D1 or D2 dopamine receptors allow addressing this question, as they share many characteristics but differ in their gene expression profiles, connections, and functional roles. We compare translating mRNAs and DNA modifications in these two populations. DNA methylation differences occur predominantly in large genomic clusters including differentially expressed genes, potentially important for D1 and D2 neurons. Decreased gene body methylation is associated with higher gene expression. Hydroxymethylation differences are more scattered and affect transcription factor binding sites, which can influence gene expression. We also find a strong genome-wide hydroxymethylation asymmetry between the two DNA strands, particularly pronounced at expressed genes and retrotransposons. These results identify novel properties of neuronal DNA modifications and unveil epigenetic characteristics of striatal projection neurons heterogeneity.

Original languageEnglish
Article number1321
JournalCommunications Biology
Volume5
Issue number1
DOIs
Publication statusPublished - 1 Dec 2022

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