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 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.
Travers
Helen
H
Chromatin and Gene Expression Group, Department of Anatomy, University of Birmingham Medical School, Birmingham, B15 2TT, United Kingdom.
Spotswood
Hugh T
HT
Moss
Paul A H
PA
Turner
Bryan M
BM
D000107:Acetylation; D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology / Q000378:metabolism*; D002087:Butyrates / Q000494:pharmacology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051379:Mice; D020033:Protein Isoforms; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism
D018952:Antigens, CD34; D002087:Butyrates; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D020033:Protein Isoforms; C012589:trichostatin A; D037761:Sirtuins; D006655:Histone Deacetylases