TY - JOUR
T1 - Expression of SCL is normal in transfusion-dependent diamond-blackfan anemia but other bHLH proteins are deficient
AU - Zhang, Min Ying
AU - Clawson, Gary A.
AU - Olivieri, Nancy F.
AU - Bell, Laurie L.
AU - Begley, C. Glenn
AU - Miller, Barbara A.
PY - 1997/9/1
Y1 - 1997/9/1
N2 - Basic helix-loop-helix proteins, which are tissue specific (SCL) or broadly expressed (E proteins), interact positively to regulate erythroid specific genes. Here, expression of SCL and two broadly expressed E proteins, E47 and HEB, was high early in erythroid differentiation and declined during maturation. Stimulation of erythroid progenitors/precursors with stem cell factor (SCF) enhanced SCL and E protein levels, one mechanism by which SCF may increase erythroid proliferation. Interactions between SCL and E proteins are competed by Id2, which binds and sequesters E proteins. Upregulation of Id2, demonstrated here late in erythroid differentiation, may downregulate genes involved in erythroid proliferation/differentiation. We examined expression of bHLH proteins in transfusion-dependent patients with Diamond- Blackfan anemia (DBA) to determine if these interactions are disrupted. In erythroblasts from patients, expression of SCL protein and mRNA was normal and SCL increased in response to SCF. However, E47 and HEB protein levels were significantly decreased. Id2 was strongly expressed in patients. Through reduction of SCL/E protein heterodimer formation, abnormal levels of bHLH transcription factors may affect expression of erythroid specific genes, such as β globin. Stimulation of Diamond-Ellackfan cells with SCF partially compensated for this defect, enhancing expression of E47, HEB, and SCL. SCF may function to increase SCL/E protein heterodimer formation, which may be one of the mechanisms through which SCF stimulates erythroid proliferation/differentiation in DBA.
AB - Basic helix-loop-helix proteins, which are tissue specific (SCL) or broadly expressed (E proteins), interact positively to regulate erythroid specific genes. Here, expression of SCL and two broadly expressed E proteins, E47 and HEB, was high early in erythroid differentiation and declined during maturation. Stimulation of erythroid progenitors/precursors with stem cell factor (SCF) enhanced SCL and E protein levels, one mechanism by which SCF may increase erythroid proliferation. Interactions between SCL and E proteins are competed by Id2, which binds and sequesters E proteins. Upregulation of Id2, demonstrated here late in erythroid differentiation, may downregulate genes involved in erythroid proliferation/differentiation. We examined expression of bHLH proteins in transfusion-dependent patients with Diamond- Blackfan anemia (DBA) to determine if these interactions are disrupted. In erythroblasts from patients, expression of SCL protein and mRNA was normal and SCL increased in response to SCF. However, E47 and HEB protein levels were significantly decreased. Id2 was strongly expressed in patients. Through reduction of SCL/E protein heterodimer formation, abnormal levels of bHLH transcription factors may affect expression of erythroid specific genes, such as β globin. Stimulation of Diamond-Ellackfan cells with SCF partially compensated for this defect, enhancing expression of E47, HEB, and SCL. SCF may function to increase SCL/E protein heterodimer formation, which may be one of the mechanisms through which SCF stimulates erythroid proliferation/differentiation in DBA.
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U2 - 10.1182/blood.v90.5.2068
DO - 10.1182/blood.v90.5.2068
M3 - Article
C2 - 9292545
AN - SCOPUS:0030923437
SN - 0006-4971
VL - 90
SP - 2068
EP - 2074
JO - Blood
JF - Blood
IS - 5
ER -