biostudies-literatureMarion-Poll LEuropean Research Council1321https://www.ebi.ac.uk/biostudies/studies/S-EPMC9715678biostudies-literatureUnknown5(1)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 Communications biologyDNA methylation and hydroxymethylation characterize the identity of D1 and D2 striatal projection neurons.PMC9715678250349Roussarie JPThermes CMarion-Poll LJaszczyszyn YGreengard PGirault JAServant NTaing LDard-Dascot CBourc'his DJordi EMulugeta EHerve DfalseDNA methylation and hydroxymethylation characterize the identity of D1 and D2 striatal projection neurons.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 2022-01-01T00:00:00Z2022 Dec2025-04-19T03:37:02.601Z2025-04-07T13:44:46.487ZS-EPMC97156783645670310.1038/s42003-022-04269-w