Global Landscape of DNA Methylation and Gene Expression in Hematopoiesis and Monocytic Differentiation

Hypothesis: Carbon-5 methylation or Carbon-5 hydroxymethylation levels of cytosine and gene expression are important factors that can direct cell fate during hematopoiesis and monocytic differentiation.;Approach: Using Affymetrix microarray technology for RNA expression analysis along with BS-sequencing and TAB-sequencing of DNA from primary human CD34+, CD33+, CD14+, monocyte derived Dendritic cells, and monocyte derived macrophages.;Results: We observe self-renewing and dividing stem cells and progenitors show expressed genes involved in pathways of cell cycle regulation and DNA replication. Transcription factors LEF-1 and SP1 have overlapping cell specific target binding sites. MiR-Let7 and miR-200 family are important in hematopoiesis and monocytic differentiation.;Global 5mC methylation does not show changes during differentiation, but RNA expression data correlated with DNA promoter methylation shows High CpG promoters (HCP) and Intermediate CpG promoters (ICP) show decreased RNA expression and opposed to unmethylated HCP and ICP promoters. 5mC or 5hmC show enrichment at some expressed genes during monocytic differentiation.;Conclusion: We conclude that gene expression changes are important factors that can help direct cell fate during differentiation. Changes in 5mC or 5hmC affect some, but not all expressed genes, so it may play a role in the regulation of a few specific genes but is not an overall critical factor that directs cell fate during hematopoiesis and monocytic differentiation.