Retroviral integration within the Fli-2 locus results in inactivation of the erythroid transcription factor NF-E2 in Friend erythroleukemias: Evidence that NF-E2 is essential for globin expression

Shi Jiang Lu, Sheldon Rowan, Maria Rosa Bani, Yaacov Ben-David

Research output: Contribution to journalArticlepeer-review

Abstract

Activation of either Fli-1 or Spi-1 members of the ets family of transcription factors as a result of retroviral insertion and mutational inactivation of the p53 tumor suppressor gene play essential roles in the multistage erythroleukemias induced in mice by various strains of Friend virus. We have previously identified another common site for provirus integration, designated Fli-2 (Friend leukemia integration 2), in some erythroleukemia clones induced either by Friend murine leukemia virus (F- MuLV) or by the polycythemia-inducing strain of Friend virus complex (FV-P). Here we show that genomic sequences adjacent to Fli-2 correspond to the coding region of the erythroid-specific DNA binding protein NF-E2 p45. In one erythroleukemia cell line the expression of NF-E2 p45 is undetectable due to proviral integration in one allele and loss of the other allele. The complete loss of NF-E2 p45 in this cell line is associated with a drastic reduction in expression of the α- and β-globin genes that were partially restored by reintroduction of the NF-E2 p45 gene. Taken together, these results provide direct evidence that NF-E2 gene is essential for globin transcription and suggest that perturbation in expression of this transcription factor may contribute to erythroleukemia progression.

Original languageEnglish
Pages (from-to)8398-8402
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number18
Publication statusPublished - Aug 30 1994

Keywords

  • gene inactivation
  • globin regulation
  • retroviral insertion

ASJC Scopus subject areas

  • General
  • Genetics

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