During differentiation, neurons experience a reorganization of DNA modification patterns within their genomes. However, the mechanisms underlying this developmental patterning and its role in defining the neuronal state are currently unclear. Here, we find that the de novo DNA methyltransferase Dnmt3a is necessary for elevated levels of 5-hydroxymethylcytosine (5hmC), a derivative of 5-methylcytosine (5mC), in olfactory sensory neurons (OSNs). Through an analysis of genome-wide 5mC and 5hmC distributions in isolated OSNs, we find that Dnmt3a-dependent 5mC and 5hmC occurs within regions of high accessibility, neural enhancers, and the transcription start sites of transcribed genes. Its loss results in the global disruption of gene expression patterns, including the upregulation of silent genes, the downregulation of mOSN-expressed genes, and the alteration of odorant-induced transcriptional responses of immediate early genes. Together, these results demonstrate that Dnmt3a is necessary to define the neuronal transcriptional state and may be broadly involved in refining expression profiles within differentiated cells. SOURCE: Stavros Lomvardas (stavros.lomvardas@ucsf.edu) -  University of California, San Francisco

Pluto Bioinformatics

GSE52464: Epigenetic and transcriptional landscapes of Dnmt3a-deficient olfactory sensory neurons