RNA-Seq profiling of mESCs and their neuronal derivatives overexpressing WT DNMT1 and DNMT1Y495C mutant form

To understand the molecular basis of neurodevelopmental abnormalities in HSAN1E disorder associated with DNMT1 Y495C mutation, we have developed transgenic mouse ES lines (R1Dnmt1 Y495C) that expresses mutant transcripts in addition to the endogenous wild-type transcripts. We also generated a transgenic cell line that overexpresses the wild-type transcripts (R1wt Dnmt1) to segregate the effects of mutant proteins. We performed transcriptome profiling of mESC lines and their neuronal derivatives using RNA-seq. Dysregulated transcripts in R1wt Dnmt1 and R1Dnmt1 Y495C mESCs and neurons were identified by comparisons with the wild-type counterpart (R1; wild-type mESC line). Gene ontology and pathway enrichment analysis were performed to identify potential pathways and key regulatory genes underlying the HSAN1E associated neurodevelopmental phenotypes.