Abstract
The molecular mechanisms governing γ-globin expression in a subset of fetal hemoglobin (α2γ2: HbF) expressing red blood cells (F-cells) and the mechanisms underlying the variability of response to hydroxyurea induced γ-globin expression in the treatment of sickle cell disease are not completely understood. Here we analyzed intra-person clonal populations of basophilic erythroblasts (baso-Es) derived from bone marrow common myeloid progenitors in serum free cultures and report the level of fetal hemoglobin production in F-cells negatively correlates with expression of BCL11A, KLF1 and TAL1. We then examined the effects of hydroxyurea on these three transcription factors and conclude that a successful induction of γ-globin includes a reduction in BCL11A, KLF1 and TAL1 expression. These data suggests that expression changes in this transcription factor network modulate γ-globin expression in F-cells during steady state erythropoiesis and after induction with hydroxyurea.
| Original language | English (US) |
|---|---|
| Article number | e0129431 |
| Journal | PLoS One |
| Volume | 10 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 8 2015 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Variation in gamma-globin expression before and after induction with hydroxyurea associated with BCL11A, KLF1 and TAL1. / Grieco, Amanda J.; Billett, Henny H.; Green, Nancy S.; Driscoll, M. Catherine; Bouhassira, Eric E.
In: PLoS One, Vol. 10, No. 6, e0129431, 08.06.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Variation in gamma-globin expression before and after induction with hydroxyurea associated with BCL11A, KLF1 and TAL1
AU - Grieco, Amanda J.
AU - Billett, Henny H.
AU - Green, Nancy S.
AU - Driscoll, M. Catherine
AU - Bouhassira, Eric E.
PY - 2015/6/8
Y1 - 2015/6/8
N2 - The molecular mechanisms governing γ-globin expression in a subset of fetal hemoglobin (α2γ2: HbF) expressing red blood cells (F-cells) and the mechanisms underlying the variability of response to hydroxyurea induced γ-globin expression in the treatment of sickle cell disease are not completely understood. Here we analyzed intra-person clonal populations of basophilic erythroblasts (baso-Es) derived from bone marrow common myeloid progenitors in serum free cultures and report the level of fetal hemoglobin production in F-cells negatively correlates with expression of BCL11A, KLF1 and TAL1. We then examined the effects of hydroxyurea on these three transcription factors and conclude that a successful induction of γ-globin includes a reduction in BCL11A, KLF1 and TAL1 expression. These data suggests that expression changes in this transcription factor network modulate γ-globin expression in F-cells during steady state erythropoiesis and after induction with hydroxyurea.
AB - The molecular mechanisms governing γ-globin expression in a subset of fetal hemoglobin (α2γ2: HbF) expressing red blood cells (F-cells) and the mechanisms underlying the variability of response to hydroxyurea induced γ-globin expression in the treatment of sickle cell disease are not completely understood. Here we analyzed intra-person clonal populations of basophilic erythroblasts (baso-Es) derived from bone marrow common myeloid progenitors in serum free cultures and report the level of fetal hemoglobin production in F-cells negatively correlates with expression of BCL11A, KLF1 and TAL1. We then examined the effects of hydroxyurea on these three transcription factors and conclude that a successful induction of γ-globin includes a reduction in BCL11A, KLF1 and TAL1 expression. These data suggests that expression changes in this transcription factor network modulate γ-globin expression in F-cells during steady state erythropoiesis and after induction with hydroxyurea.
UR - http://www.scopus.com/inward/record.url?scp=84936804259&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84936804259&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0129431
DO - 10.1371/journal.pone.0129431
M3 - Article
C2 - 26053062
AN - SCOPUS:84936804259
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 6
M1 - e0129431
ER -