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Pleiotropic role of histone deacetylases in the regulation of human adult erythropoiesis
Author(s) -
Yamamura Kentaro,
Ohishi Kohshi,
Katayama Naoyuki,
Yu Zhaocai,
Kato Keizo,
Masuya Masahiro,
Fujieda Atsushi,
Sugimoto Yuka,
Miyata Eri,
Shibasaki Tetsunori,
Heike Yuji,
Takaue Yoichi,
Shiku Hiroshi
Publication year - 2006
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2006.06275.x
Subject(s) - erythropoiesis , trichostatin a , biology , depsipeptide , haematopoiesis , stem cell factor , microbiology and biotechnology , histone , acetylation , histone deacetylase , stem cell , cancer research , biochemistry , anemia , medicine , gene
Summary Histone acetylation and deacetylation play fundamental roles in transcriptional regulation. We investigated the role of histone deacetylases (HDACs) in human adult haematopoiesis, using the structurally distinct HDAC inhibitors FK228 (depsipeptide) and Trichostatin A. When CD34 + cells were cultured with interleukin (IL)‐3 or stem cell factor (SCF) + IL‐3, FK228 (0·5 ng/ml) specifically enhanced the generation of immature erythroid cells with a CD36 + glycophorin A (GPA) low phenotype. In semisolid cultures, FK228 promoted the formation of erythroid colonies by CD34 + cells with IL‐3 and SCF + IL‐3. Furthermore, upon exposure to FK228, CD34 + cell‐derived CD36 + GPA − cells were induced to form erythroid colonies with IL‐3 alone. Conversely, FK228 inhibited the generation of CD36 + GPA high relatively mature erythroid cells from CD34 + cells in the presence of erythropoietin (EPO) and SCF + EPO. FK228 suppressed the EPO‐mediated survival of CD36 + GPA low/‐ and CD36 + GPA high cells and induced their apoptosis. Similar effects were observed for trichostatin A in the generation of erythroid cells in IL‐3‐ and EPO‐containing cultures. These data suggest that HDACs negatively regulate the IL‐3‐mediated growth of early erythroid precursors by suppressing their responsiveness to IL‐3, while playing an important role in EPO‐mediated differentiation and survival of erythroid precursors. Our data revealed that HDACs have diverse functions in human adult erythropoiesis.