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

Mol Cell Biol. 2000 Oct;20(20):7662-72. doi: 10.1128/MCB.20.20.7662-7672.2000.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Codon, Initiator / genetics
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism*
  • Dimerization
  • Fetal Blood / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Globins / genetics*
  • Globins / metabolism
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • K562 Cells
  • Macromolecular Substances
  • Molecular Sequence Data
  • Precipitin Tests
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation*
  • Two-Hybrid System Techniques

Substances

  • 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