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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 gamma -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 gamma  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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