title: Spi-1 and Fli-1 directly activate common target genes involved in ribosome biogenesis in Friend erythroleukemic cells.
abstract: Spi-1 and Fli-1 are ETS transcription factors recurrently deregulated in mouse erythroleukemia induced by Friend viruses. Since they share the same core DNA binding site, we investigated whether they may contribute to erythroleukemia by common mechanisms. Using inducible knockdown, we demonstrated that Fli-1 contributes to proliferation, survival, and differentiation arrest of erythroleukemic cells harboring an activated fli-1 locus. Similarly, we used inducible Fli-1 knockdown and either hexamethylenebisacetamide (HMBA)- or small interfering RNA-mediated Spi-1 knockdown to investigate their respective contributions in erythroleukemic cells harboring an activated spi-1 locus. In these cells, simple or double knockdown of both Spi-1 and Fli-1 additively contributed to induce proliferation arrest and differentiation. Transcriptome profiling revealed that virtually all transcripts affected by both Fli-1 knockdown and HMBA are affected in an additive manner. Among these additively downregulated transcripts, more than 20% encode proteins involved in ribosome biogenesis, and conserved ETS binding sites are present in their gene promoters. Through chromatin immunoprecipitation, we demonstrated the association of Spi-1 and Fli-1 on these promoters in Friend erythroleukemic cells. These data lead us to propose that the oncogenicity of Spi-1, Fli-1, and possibly other ETS transcription factors may involve their ability to stimulate ribosome biogenesis.
authors.affiliation: Université Lyon 1, Lyon F-69003, France.
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Juban
authors.forename: Guillaume
authors.initials: G
authors.lastname: Giraud
authors.forename: Boris
authors.initials: B
authors.lastname: Guyot
authors.forename: Stéphane
authors.initials: S
authors.lastname: Belin
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Diaz
authors.forename: Joëlle
authors.initials: J
authors.lastname: Starck
authors.forename: Christel
authors.initials: C
authors.lastname: Guillouf
authors.forename: Françoise
authors.initials: F
authors.lastname: Moreau-Gachelin
authors.forename: François
authors.initials: F
authors.lastname: Morlé
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation; D005622:Friend murine leukemia virus / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000502:physiology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D051789:Proto-Oncogene Protein c-fli-1; C086597:lambda Spi-1