Publication: Blood. 122(17): 2978-2986.
Published Date: September 12, 2013
Examines the role DNA methylation of regulatory elements plays in the performance of the Runx1 promoter switch during hematopoietic stem cell (HSC) development.
In HSCs, the regulation of transcription factor Runx1 is controlled by two promoters (P1 and P2) and one enhancer element that operate together to drive development. However, the mechanism responsible for the promoter switch’s function is poorly understood. DNA methylation, a regulatory mechanism, is important for lineage commitment in hematopoietic systems, but its contribution to the Runx1 promoter switch had not been explored. The authors examined the DNA methylation status of Runx1 regulatory elements at various stages in hematopoietic development and differentiation, and found that a gradual decrease in methylation of P1 is correlated with definitive HSCs during development while P2 is consistently unmethylated. These data suggest that the Runx1 P1 promoter is a novel tissue-specific differentially methylated region.