Impairment of human terminal erythroid differentiation by histone deacetylase 5 deficiency

Histone deacetylases (HDACs) are a group of enzymes catalyzing the removal of acetyl groups from histone and non-histone proteins. HDACs have been shown to play diverse functions in a wide range of biological processes. However, their roles in mammalian erythropoiesis remain to be fully defined. We show here that of the eleven classic HDAC family members, six of them (HDAC 1,2,3 and HDAC 5,6,7) are expressed in human erythroid cells with HDAC5 significantly up regulated during terminal erythroid differentiation. Knockdown of HDAC5 in human CD34+ cells followed by erythroid cell culture led to increased apoptosis, decreased chromatin condensation, and impaired enucleation of erythroblasts. ATAC-seq and RNA-seq analyses between normal erythropoiesis and HDAC5 knockdown erythropoiesis