Blood, Vol. 92 No. 11 (December 1), 1998:
pp. 4383-4393
Coinduction of Embryonic and Adult-Type Globin mRNAs by Sodium
Butyrate and Trichostatin A in Two Murine Interleukin-3-Dependent Bone
Marrow-Derived Cell Lines
Kimiko Ishiguro and
Alan C. Sartorelli
From the Department of Pharmacology and Developmental Therapeutics
Program, Cancer Center, Yale University School of Medicine, New Haven,
CT.
Using an RNase protection assay, globin mRNA species expressed in
clones derived from Ba/F3 and B6SUtA cells transfected with the
erythropoietin receptor (EpoR) and selected with erythropoietin (Epo)
were compared with globin mRNA species induced in corresponding parental cells by sodium butyrate (SB) and trichostatin A (TSA). 
Major/minor- and 
-1/-2-globin
mRNAs were the major species, with trace amounts of 
-globin mRNA,
formed in Epo-stimulated EpoR+ Ba/F3 clones, whereas SB
and TSA allowed expression of all species of globin mRNAs, ie, ,
h1, major/minor, 
, and -1/-2,
in parental Ba/F3 cells. In contrast, - and -1/-2-globin
mRNAs were the major species present in Epo-stimulated EpoR+ B6SUtA clones, whereas SB and TSA activated -,
h1-, S/T-, and -1/-2-globin
genes in parental B6SUtA cells; -globin mRNA was not detected in SB-
and TSA-treated B6SUtA cells. Because TSA is a specific inhibitor of
histone deacetylase, the mimicry of action exhibited by SB and TSA
suggests that the effects of SB are mediated through its ability to
inhibit histone deacetylase and that histone deacetylase is an integral
part of the repression of globin genes in these
interleukin-3-dependent cells. Efficient coinduction of embryonic and
adult types of globin mRNA in bone marrow cell lines derived from adult
mice indicates that adult hematopoietic precursors possess an embryonic
nature. These cell lines are useful models to study the mechanism(s) of
developmental globin gene switching.
