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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Codon, Initiator / genetics
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DNA / genetics
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DNA / metabolism
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DNA-Binding Proteins / metabolism*
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Dimerization
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Fetal Blood / metabolism*
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Gene Expression Profiling
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Gene Expression Regulation, Developmental*
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Globins / genetics*
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Globins / metabolism
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Hematopoietic Stem Cells / metabolism
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Humans
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K562 Cells
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Macromolecular Substances
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Molecular Sequence Data
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Precipitin Tests
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Protein Binding
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA-Binding Proteins
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Recombinant Fusion Proteins
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcriptional Activation*
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Two-Hybrid System Techniques
Substances
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Codon, Initiator
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DNA-Binding Proteins
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Macromolecular Substances
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RNA, Messenger
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RNA-Binding Proteins
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Recombinant Fusion Proteins
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TFCP2 protein, human
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Transcription Factors
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enhancer-binding protein NF-E4
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Globins
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DNA