Induction of human fetal globin gene expression by a novel erythroid factor, NF-E4.

Abstract	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.
Authors	W Zhou, D R Clouston, X Wang, L Cerruti, J M Cunningham, S M Jane
Journal	Molecular and cellular biology (Mol Cell Biol) Vol. 20 Issue 20 Pg. 7662-72 (Oct 2000) ISSN: 0270-7306 [Print] United States
PMID	11003662 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Codon, Initiator DNA-Binding Proteins Macromolecular Substances RNA, Messenger RNA-Binding Proteins Recombinant Fusion Proteins TFCP2 protein, human Transcription Factors enhancer-binding protein NF-E4 Globins DNA
Topics	Amino Acid Sequence Base Sequence Codon, Initiator (genetics) DNA (genetics, metabolism) DNA-Binding Proteins (metabolism) Dimerization Fetal Blood (metabolism) Gene Expression Profiling Gene Expression Regulation, Developmental Globins (genetics, metabolism) Hematopoietic Stem Cells (metabolism) Humans K562 Cells Macromolecular Substances Molecular Sequence Data Precipitin Tests Protein Binding RNA, Messenger (genetics, metabolism) RNA-Binding Proteins Recombinant Fusion Proteins Transcription Factors (chemistry, genetics, metabolism) Transcriptional Activation Two-Hybrid System Techniques

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