TY - JOUR
T1 - Sox6 enhances erythroid differentiation in human erythroid progenitors
AU - Cantù, Claudio
AU - Ierardi, Rossella
AU - Alborelli, Ilaria
AU - Fugazza, Cristina
AU - Cassinelli, Letizia
AU - Piconese, Silvia
AU - Bosè, Francesca
AU - Ottolenghi, Sergio
AU - Ferrari, Giuliana
AU - Ronchi, Antonella
PY - 2011/3/31
Y1 - 2011/3/31
N2 - Sox6 belongs to the Sry (sex-determining region Y)-related high-mobility-group-box family of transcription factors, which control cell-fate specification of many cell types. Here, we explored the role of Sox6 in human erythropoiesis by its overexpression both in the erythroleukemic K562 cell line and in primary erythroid cultures from human cord blood CD34+ cells. Sox6 induced significant erythroid differentiation in both models. K562 cells underwent hemoglobinization and, despite their leukemic origin, died within 9 days after transduction; primary erythroid cultures accelerated their kinetics of erythroid maturation and increased the number of cells that reached the final enucleation step. Searching for direct Sox6 targets, we found SOCS3 (suppressor of cytokine signaling-3), a known mediator of cytokine response. Sox6 was bound in vitro and in vivo to an evolutionarily conserved regulatory SOCS3 element, which induced transcriptional activation. SOCS3 overexpression in K562 cells and in primary erythroid cells recapitulated the growth inhibition induced by Sox6, which demonstrates that SOCS3 is a relevant Sox6 effector.
AB - Sox6 belongs to the Sry (sex-determining region Y)-related high-mobility-group-box family of transcription factors, which control cell-fate specification of many cell types. Here, we explored the role of Sox6 in human erythropoiesis by its overexpression both in the erythroleukemic K562 cell line and in primary erythroid cultures from human cord blood CD34+ cells. Sox6 induced significant erythroid differentiation in both models. K562 cells underwent hemoglobinization and, despite their leukemic origin, died within 9 days after transduction; primary erythroid cultures accelerated their kinetics of erythroid maturation and increased the number of cells that reached the final enucleation step. Searching for direct Sox6 targets, we found SOCS3 (suppressor of cytokine signaling-3), a known mediator of cytokine response. Sox6 was bound in vitro and in vivo to an evolutionarily conserved regulatory SOCS3 element, which induced transcriptional activation. SOCS3 overexpression in K562 cells and in primary erythroid cells recapitulated the growth inhibition induced by Sox6, which demonstrates that SOCS3 is a relevant Sox6 effector.
UR - http://www.scopus.com/inward/record.url?scp=79953693567&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79953693567&partnerID=8YFLogxK
U2 - 10.1182/blood-2010-04-282350
DO - 10.1182/blood-2010-04-282350
M3 - Article
C2 - 21263153
AN - SCOPUS:79953693567
VL - 117
SP - 3669
EP - 3679
JO - Blood
JF - Blood
SN - 0006-4971
IS - 13
ER -