Human CD34+ Hematopoietic Progenitor Cells Hyperacetylate Core Histones in Response to Sodium Butyrate, but Not Trichostatin A

Cells positive for the cell surface marker CD34 from bone marrow or umbilical cord blood form a subset of quiescent, hematopoetic precursors that can establish human hematopoesis in immunodeficient mice and can progress down various differentiation pathways in vitro. They provide a valuable model sy...

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Bibliographic Details
Published in:Experimental cell research 2002-11, Vol.280 (2), p.149-158
Main Authors: Travers, Helen, Spotswood, Hugh T., Moss, Paul A.H., Turner, Bryan M.
Format: Article
Language:English
Subjects:
Acetylation
Animals
Antigens, CD34 - immunology
Antigens, CD34 - metabolism
Butyrates - pharmacology
Cells, Cultured
chromatin
deacetylase inhibitors
deacetylases
Enzyme Inhibitors - pharmacology
hematopoiesis
Hematopoietic Stem Cells - drug effects
Hematopoietic Stem Cells - physiology
histone acetylation
Histone Deacetylase Inhibitors
Histone Deacetylases - genetics
Histone Deacetylases - metabolism
Histones - metabolism
Humans
Hydroxamic Acids - pharmacology
Mice
Protein Isoforms
Sirtuins - genetics
Sirtuins - metabolism
trichostatin A
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Summary:Cells positive for the cell surface marker CD34 from bone marrow or umbilical cord blood form a subset of quiescent, hematopoetic precursors that can establish human hematopoesis in immunodeficient mice and can progress down various differentiation pathways in vitro. They provide a valuable model system in which progression from quiescent to cycling to differentiated states can be linked to changes in chromatin and histone modification. We have used the deacetylase inhibitor sodium butyrate to show that turnover of histone H4 acetates is rapid and comparable in quiescent and cycling CD34+ cells from human umbilical cord blood (CD34+ UBC). Surprisingly, the widely used inhibitor trichostatin A (TSA) had little (cycling cells) or no (quiescent cells) effect on H4 acetylation in CD34+ UBC. Among five cell types examined, CD34+ UBC were unique in expressing all (putative) deacetylases tested (HDAC1, -2, -3, -4, -6, -7, and -8 and SIRT1-4), but no single deacetylase correlated with their TSA resistance. Also, HDAC1, -2, -3, and -6 complexes isolated from CD34+ UBC by immunoprecipitation were all inhibited by TSA in vitro. Thus, TSA resistance of CD34+ UBC is not due to acquired or intrinsic TSA resistance of their deacetylases and may reflect an enhanced ability to process the drug.
ISSN:0014-4827
1090-2422
DOI:10.1006/excr.2002.5632