Wild-type egr1/Krox24 promotes and dominant-negative mutants inhibit, pluripotent differentiation of p19 embryonal carcinoma cells.
The zinc-finger transcription factor Krox24 was analysed for its role in differentiation in P19 embryonal carcinoma cells. Reciprocal dominant negative mutants consisting of Krox24 deleted for a crucial region of the zinc-finger domain (delta Krox24) or of the zinc-finger region alone (delta Krox24Zf) abolished the activation of transcription by Krox24 in P19 cells. Expression of Krox24 led to spontaneous differentiation of P19 cells in a lineage-independent fashion. Krox24 transfected populations, as well as individual clones randomly picked from them, displayed a wide array of diverse morphologies and expressed markers characteristic of a variety of differentiated cells. The dominant negative mutants blocked differentiation of P19 cells. We conclude that expression of Krox24 is sufficient for pluripotent differentiation of embryonal carcinoma cells, and that expression of Krox24 or other egr family members is essential to this process.
Lanoix
J
J
Institut du cancer de Montréal/Centre de Recherche Louis Charles Simard, Québec, Canada.
Mullick
A
A
He
Y
Y
Bravo
R
R
Skup
D
D
D019943:Amino Acid Substitution; D000818:Animals; D018236:Carcinoma, Embryonal / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D051379:Mice; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000502:physiology; D017384:Sequence Deletion; D018243:Teratocarcinoma / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D016335:Zinc Fingers / Q000502:physiology*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D014212:Tretinoin