Chromatin assembly factor HIRA is essential for the maintenance of hematopoiesis

HIRA is a histone chaperone that deposits the histone variant H3.3 in transcriptionally active genes. HIRA is essential for mouse development, as the standard knockout (KO) results in early embryonic death. However, the role of HIRA in hematopoiesis is poorly understood. We investigated the effect of Hira KO on hematopoiesis using Vav-Cre Loxp system. We show that Hira KO dramatically reduces bone marrow LSK cells, resulting in anemia, thrombopenia and severe, combined immunodeficiency. To investigate the molecular mechanisms, RNA-seq and ATAC-Seq were performed using LSK cells isolated from WT and Hira conditional KO mice. Overall design: Examination of the alteration of gene expression and chromatin accessibilty in LSK (Lin-Sca1+cKit+) cells sorted from WT or Hira KO bone marrow cells by FACS