Enhancer dynamics in blood cell development

Together with the Andersson/Ekwall groups at Karolinska Institute and the FANTOM consortium, we have analyzed enhancer dynamcis and methylation in granulopoiesis (red blood cell development) - published in Blood:

Rönnerblad et al, Analysis of the DNA methylome and transcriptome in granulopoiesis reveal timed changes and dynamic enhancer methylation

In development, epigenetic mechanisms such as DNA methylation have been suggested to provide a cellular memory to maintain multipotency but also stabilize cell fate decisions and direct lineage restriction. In this study, we set out to characterize changes in DNA methylation and gene expression during granulopoiesis using 4 distinct cell populations ranging from the oligopotent common myeloid progenitor stage to terminally differentiatedn eutrophils. We observed that differentially methylated sites (DMSs) generally show decreased methylation during granulopoiesis. Methylation appears to change at specific differentiation stages and overlap with changes in transcription and activity of key hematopoietic transcription factors. DMSs were preferentially located in areas distalto CG dinucleotides islands and shores. Also, DMSs were overrepresented in enhancer elements and enriched in enhancers that become active during differentiation. Overall,this study depicts in detail the epigenetic and transcriptional changes that occur duringgranulopoiesis and supports the role of DNA methylation as a regulatory mechanism inblood cell differentiation.