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Molecular and Cellular Biology, October 2000, p. 7662-7672, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Induction of Human Fetal Globin Gene Expression by
a Novel Erythroid Factor, NF-E4
Wenlai
Zhou,1
David R.
Clouston,1
Xi
Wang,2
Loretta
Cerruti,1
John M.
Cunningham,2 and
Stephen M.
Jane1,*
Rotary Bone Marrow Research Laboratory, Royal Melbourne
Hospital Research Foundation, Parkville, Victoria,
Australia,1 and Division of
Experimental Hematology, St. Jude Children's Research Hospital,
Memphis, Tennessee2
Received 23 May 2000/Returned for modification 21 June
2000/Accepted 18 July 2000
The stage selector protein (SSP) is a heteromeric complex involved
in preferential expression of the human
-globin genes in
fetal-erythroid cells. We have previously identified the ubiquitous transcription factor CP2 as a component of this complex. Using the
protein dimerization domain of CP2 in a yeast two-hybrid screen, we
have cloned a novel gene, NF-E4, encoding the tissue-restricted component of the SSP. NF-E4 and CP2 coimmunoprecipitate from extract derived from a fetal-erythroid cell line, and antiserum to NF-E4 ablates binding of the SSP to the
promoter. NF-E4 is expressed in
fetal liver, cord blood, and bone marrow and in the K562 and HEL cell
lines, which constitutively express the fetal globin genes. Enforced
expression of NF-E4 in K562 cells and primary erythroid progenitors
induces endogenous fetal globin gene expression, suggesting a possible
strategy for therapeutic intervention in the hemoglobinopathies.
*
Corresponding author. Mailing address: Rotary Bone
Marrow Research Laboratory, Royal Melbourne Hospital Research
Foundation, c/o Royal Melbourne Hospital Post Office, Grattan St.,
Parkville, VIC 3050, Australia. Phone: 61-3-93428641. Fax:
61-3-93428634. E-mail: jane{at}wehi.edu.au.
Molecular and Cellular Biology, October 2000, p. 7662-7672, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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