GSE40539
Genome-wide DNA hydroxymethylation changes are associated with neurodevelopmental genes in the developing human brain
5-hydroxymethylcytosine (5-hmC) is a  newly discovered  modified form of cytosine that has been suspected to  be an important epigenetic modification  in  neurodevelopment. While  DNA  methylation dynamics  have already been implicated during  neurodevelopment, little is known about hydroxymethylation in this process. Here we report DNA hydroxymethylation dynamics during  cerebellum development in  the  human brain.  Overall, we find a positive correlation  between 5-hmC levels and cerebellum development. Genome-wide profiling reveals that 5-hmC is highly enriched  on specific gene regions, including  exons and especially the  untranslated regions (UTRs), but it is depleted on introns and intergenic regions. Furthermore, we have identified fetus-specific and adult-specific differentially hydroxymethylated regions (DhMRs), most of which overlap with genes and  CpG island shores. Surprisingly, during development DhMRs are highly enriched in genes encoding mRNAs that can be regulated by fragile X mental retardation protein (FMRP), some of which are disrupted in autism, as well as in many known autism genes. Our results suggest that 5-hmC-mediated epigenetic regulation  may  broadly impact the development of  the  human brain, and  its dysregulation could  contribute to the molecular pathogenesis of neurodevelopmental disorders. Overall design: We generated comprehensive genome-wide profiles of 5hmC in human cerebellum.