Expression Levels of Histone Deacetylases Determine the Cell Fate of Hematopoietic Progenitors

• Published in: The Journal of biological chemistry Vol. 284; no. 44; pp. 30673 - 30683
• Main Authors: Wada, Taeko, Kikuchi, Jiro, Nishimura, Noriko, Shimizu, Rumi, Kitamura, Toshio, Furukawa, Yusuke
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.10.2009; American Society for Biochemistry and Molecular Biology
• Subjects: Bone Marrow Cells - cytology; CCAAT-Binding Factor - physiology; Cell Differentiation; Cell Line, Tumor; Cells, Cultured; GATA1 Transcription Factor - physiology; Gene Expression Regulation - physiology; Hematopoiesis; Hematopoietic Stem Cells - cytology; Histone Deacetylase 1 - analysis; Histone Deacetylase 1 - genetics; Histone Deacetylase 1 - physiology; Histone Deacetylases - analysis; Histone Deacetylases - genetics; Histone Deacetylases - physiology; Humans; Leukemia, Myeloid; Molecular Basis of Cell and Developmental Biology; Myeloid Cells; Transcription, Genetic
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109.042242

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.