Expression levels of histone deacetylases determine the cell fate of hematopoietic progenitors.
Histone deacetylases (HDACs) are globally implicated in the growth and differentiation of mammalian cells; however, relatively little is known about their specific roles in hematopoiesis. In this study, we investigated the expression of HDACs in human hematopoietic cells and their functions during hematopoiesis. The expression of HDACs was very low in hematopoietic progenitor cells, which was accompanied by histone hyperacetylation. HDACs were detectable in more differentiated progenitors and erythroid precursors but down-regulated in mature myeloid cells especially granulocytes. In contrast, acute myeloid leukemias showed HDAC overexpression and histone hypoacetylation. Transcription of the HDAC1 gene was repressed by CCAAT/enhancer binding proteins during myeloid differentiation, and activated by GATA-1 during erythro-megakaryocytic differentiation. Small interfering RNA-mediated knockdown of HDAC1 enhanced myeloid differentiation in immature hematopoietic cell lines and perturbed erythroid differentiation in progenitor cells. Myeloid but not erythro-megakaryocytic differentiation was blocked in mice transplanted with HDAC1-overexpressing hematopoietic progenitor cells. These findings suggest that HDAC is not merely an auxiliary factor of genetic elements but plays a direct role in the cell fate decision of hematopoietic progenitors.
Wada
Taeko
T
Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical School, Tochigi 329-0498, Japan.
Kikuchi
Jiro
J
Nishimura
Noriko
N
Shimizu
Rumi
R
Kitamura
Toshio
T
Furukawa
Yusuke
Y
D001854:Bone Marrow Cells / Q000166:cytology; D023081:CCAAT-Binding Factor / Q000502:physiology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D050982:GATA1 Transcription Factor / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D056284:Histone Deacetylase 1 / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D006655:Histone Deacetylases / Q000032:analysis / Q000235:genetics / Q000502:physiology; D006801:Humans; D007951:Leukemia, Myeloid; D022423:Myeloid Cells; D014158:Transcription, Genetic
D023081:CCAAT-Binding Factor; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases