Spi-1/PU.1 Is a positive regulator of the Fli-1 gene involved in inhibition of erythroid differentiation in friend erythroleukemic cell lines

Joëlle Starck, Alexandre Doubeikovski, Sandrine Sarrazin, Colette Gonnet, Govinda Rao, Arthur I. Skoultchi, Jacqueline Godet, Isabelle Dusanter-Fourt, François Morle

Research output: Contribution to journalArticle

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Abstract

Spi-1/PU.1 and Fli-1 are two members of the ETS family of transcription factors whose expression is deregulated by proviral insertion in most erythroleukemic cell lines induced by the spleen focus-forming virus (SFFV) and Friend murine leukemia virus (F-MuLV) components of the Friend viral complex, respectively. In this study, we present evidence that transcription of the Fli-1 gene is positively regulated by Spi-1/PU.1 in SFFV-transformed cell lines: (i) all SFFV-transformed cell lines expressing Spi-1/PU.1 are characterized by a specific pattern of Fli-1 gene transcripts initiated in the -200 region instead of position -400 as reported for F-MuLV-transformed cell lines; (ii) these Fli-1 transcripts initiated in the -200 region are downregulated in parallel with that of Spi-1/PU.1 during hexamethylenebisacetamide (HMBA) induced differentiation; and (iii) Fli-1 transcription is upregulated in SFFV cells lines following stable transfection of a Spi-1/PU.1 expression vector. Furthermore, we found by transient transfection assays that the -270/-41 region of the Fli-1 gene displays promoter activity which is transactivated by Spi-1/PU.1. This promoter is strictly dependent on the integrity of two highly conserved ETS DNA binding sites that bind the Spi-1/PU.1 protein in vitro. Finally, we show that transfection of constitutive or inducible Fli-1 expression vectors in SFFV-transformed cells inhibits their erythroid differentiation induced by HMBA. Overall, these data indicate that Fli-1 is a target gene of the Spi- 1/PU.1 transcription factor in SFFV-transformed cell lines. We further suggest that deregulated synthesis of Fli-1 may trigger a common mechanism contributing to erythroleukemia induced by either SFFV or F-MuLV.

Original languageEnglish (US)
Pages (from-to)121-135
Number of pages15
JournalMolecular and Cellular Biology
Volume19
Issue number1
StatePublished - Jan 1999

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Spleen Focus-Forming Viruses
Cell Line
Transformed Cell Line
Friend murine leukemia virus
Genes
Transfection
Transcription Factors
Viral Structures
Leukemia, Erythroblastic, Acute
lambda Spi-1
Inhibition (Psychology)
Down-Regulation
Binding Sites

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Spi-1/PU.1 Is a positive regulator of the Fli-1 gene involved in inhibition of erythroid differentiation in friend erythroleukemic cell lines. / Starck, Joëlle; Doubeikovski, Alexandre; Sarrazin, Sandrine; Gonnet, Colette; Rao, Govinda; Skoultchi, Arthur I.; Godet, Jacqueline; Dusanter-Fourt, Isabelle; Morle, François.

In: Molecular and Cellular Biology, Vol. 19, No. 1, 01.1999, p. 121-135.

Research output: Contribution to journalArticle

Starck, J, Doubeikovski, A, Sarrazin, S, Gonnet, C, Rao, G, Skoultchi, AI, Godet, J, Dusanter-Fourt, I & Morle, F 1999, 'Spi-1/PU.1 Is a positive regulator of the Fli-1 gene involved in inhibition of erythroid differentiation in friend erythroleukemic cell lines', Molecular and Cellular Biology, vol. 19, no. 1, pp. 121-135.
Starck, Joëlle ; Doubeikovski, Alexandre ; Sarrazin, Sandrine ; Gonnet, Colette ; Rao, Govinda ; Skoultchi, Arthur I. ; Godet, Jacqueline ; Dusanter-Fourt, Isabelle ; Morle, François. / Spi-1/PU.1 Is a positive regulator of the Fli-1 gene involved in inhibition of erythroid differentiation in friend erythroleukemic cell lines. In: Molecular and Cellular Biology. 1999 ; Vol. 19, No. 1. pp. 121-135.
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abstract = "Spi-1/PU.1 and Fli-1 are two members of the ETS family of transcription factors whose expression is deregulated by proviral insertion in most erythroleukemic cell lines induced by the spleen focus-forming virus (SFFV) and Friend murine leukemia virus (F-MuLV) components of the Friend viral complex, respectively. In this study, we present evidence that transcription of the Fli-1 gene is positively regulated by Spi-1/PU.1 in SFFV-transformed cell lines: (i) all SFFV-transformed cell lines expressing Spi-1/PU.1 are characterized by a specific pattern of Fli-1 gene transcripts initiated in the -200 region instead of position -400 as reported for F-MuLV-transformed cell lines; (ii) these Fli-1 transcripts initiated in the -200 region are downregulated in parallel with that of Spi-1/PU.1 during hexamethylenebisacetamide (HMBA) induced differentiation; and (iii) Fli-1 transcription is upregulated in SFFV cells lines following stable transfection of a Spi-1/PU.1 expression vector. Furthermore, we found by transient transfection assays that the -270/-41 region of the Fli-1 gene displays promoter activity which is transactivated by Spi-1/PU.1. This promoter is strictly dependent on the integrity of two highly conserved ETS DNA binding sites that bind the Spi-1/PU.1 protein in vitro. Finally, we show that transfection of constitutive or inducible Fli-1 expression vectors in SFFV-transformed cells inhibits their erythroid differentiation induced by HMBA. Overall, these data indicate that Fli-1 is a target gene of the Spi- 1/PU.1 transcription factor in SFFV-transformed cell lines. We further suggest that deregulated synthesis of Fli-1 may trigger a common mechanism contributing to erythroleukemia induced by either SFFV or F-MuLV.",
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AU - Doubeikovski, Alexandre

AU - Sarrazin, Sandrine

AU - Gonnet, Colette

AU - Rao, Govinda

AU - Skoultchi, Arthur I.

AU - Godet, Jacqueline

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AU - Morle, François

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