PGE2 alters chromatin through H2A.Zvariant   enhancer nucleosome modification  to promote hematopoietic stem cell fate (ATAC-Seq)
Hematopoietic stem and progenitor cells (HSPCs) need  require tight transcriptional regulation. In-depth knowledge on how epigenetic mechanisms  regulate chromatin landscape in order to control gene expression,  particularly in response to external stimuli, will be key to understand the pathogenesis of  hematologic disorders and improve blood stem cell-based therapies. Prostaglandin E2 (PGE2) and  its metabolically resistant analog 16,16-dimethyl-PGE2 (dmPGE2) were previously identified as a  potent external stimulus to enhance HSPC engraftment. PGE2 has been evaluated in various  clinical trials to improve engraftment of stem cells. To understand the mechanism of gene  expression changes, Wwe identified that dmPGE2 mediates chromatin flexibility at HSPC-specific  enhancers through histone-variant H2A.Z acetylation to promote master transcription factor (TF)  binding and reinforce expression of genes involved in stem cell fate and engraftment. Overall design: ATAC-seq was performed, after a 2hr pulse with either dmPGE2 or DMSO on human CD34+ HSPCs