title: A putative role for histone deacetylase in the differentiation of human erythroid cells.
abstract: Histone acetylation controls the expression of specific genes in eukaryotic cells. We investigated the role of histone deacetylases (HDACs) in the differentiation of human erythroid cells, using pharmacological approaches. When CD36+ erythroid precursor cells, generated from CD34+ cells with stem cell factor, flt-3 ligand, thrombopoietin, interleukin-3, interleukin-6, and erythropoietin, were cultured with an HDAC inhibitor FK228 (depsipeptide) at a specified dose in the presence of erythropoietin, their differentiation was inhibited, as determined by the expression of CD45 and glycophorin A. Addition of the same dose of FK228 to cultures did not affect the growth of CD36+ cells. Regardless of the presence or absence of FK228, cultured CD36+ cells displayed similar proliferation kinetics. Analysis of acetylated histones revealed that FK228 upregulated the acetylation status of histones H3 and H4 in CD36+ cells. The inhibition of CD36+ cell differentiation was restored by removal of FK228 from the culture, indicating that the modification of CD36+ cell differentiation by FK228 is reversible. Furthermore, interference with histone deacetylation by FK228 inhibited the generation of CD36+ erythroid cells from CD34+ hematopoietic progenitor cells. Our results indicate the possible involvement of HDACs in human erythropoiesis, especially the regulation of erythroid cell differentiation.
authors.affiliation: Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fujieda
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Katayama
authors.forename: Kohshi
authors.initials: K
authors.lastname: Ohishi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamamura
authors.forename: Tetsunori
authors.initials: T
authors.lastname: Shibasaki
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Eri
authors.initials: E
authors.lastname: Miyata
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Masuya
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Ueda
authors.forename: Hidenori
authors.initials: H
authors.lastname: Nakajima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
mesh_terms: D000107:Acetylation / Q000187:drug effects; D018955:CD36 Antigens / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D047630:Depsipeptides / Q000494:pharmacology; D041905:Erythroid Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004921:Erythropoietin / Q000494:pharmacology; D005434:Flow Cytometry; D006021:Glycophorins / Q000032:analysis; D006655:Histone Deacetylases / Q000378:metabolism / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D013997:Time Factors
chemical_list: D018955:CD36 Antigens; D047630:Depsipeptides; D006021:Glycophorins; D006657:Histones; D004921:Erythropoietin; C087123:romidepsin; D017493:Leukocyte Common Antigens; D006655:Histone Deacetylases