SETD5 Modulates Hematopoietic Stem Cells Homeostasis By Mediating RNA Polymerase II Pausing in Cooperation with HCF-1

Stem cells maintain their self-renewal and differentiation through tight regulation of gene expression patterns at the transcriptional and epigenetic levels. SETD5 is a member of SET domain-containing histone lysine methyltransferase family. Its mutations were identified as the genetic causes of neurodevelopmental disorders, although SETD5 has been shown to lack methyltransferase activity in several studies. Deletion of Setd5 resulted in embryonic lethality at E10.5-11.5 with reduced cell number of CD41 + early hematopoietic cells in the blood island, while the role of SETD5 in adult stem cell, especially in hematopoietic stem cells (HSC) remains unexplored.