DNA methylation/hydroxymethylation regulate gene expression and alternative splicing during terminal granulopoiesis

Aim: To determine whether epigenetic modifications of DNA regulate gene expression and alternative splicing during terminal granulopoiesis. Materials & methods: Using whole genome bisulfite sequencing, reduced representation hydroxymethylation profiling and mRNA sequencing, we compare changes in DNA methylation, DNA hydroxymethylation, gene expression and alternative splicing in mouse promyelocytes and granulocytes. Results & conclusion: We show reduced DNA methylation at the promoters and enhancers of key granulopoiesis genes, indicating a regulatory role in the activation of lineage-specific genes during differentiation. Notably, increased DNA hydroxymethylation in exons is associated with preferential inclusion of specific exons in granulocytes. Overall, DNA methylation and hydroxymethylation changes at particular genomic loci may play specific roles in gene regulation or alternative splicing during terminal granulopoiesis. Data deposition: Whole genome bisulfite sequencing of mouse promyelocytes and granulocytes: Gene Expression Omnibus (GSE85517); mRNA sequencing of mouse promyelocytes and granulocytes: Gene Expression Omnibus (GSE48307); reduced representation 5-hydroxymethylation profiling of mouse promyelocytes and granulocytes: Bioproject (PRJNA495696).