Gene control in germinal differentiation: RNF6, a transcription regulatory protein in the mouse sertoli cell.
In mouse Sertoli cells, transcription of the Inha gene encoding the alpha subunit of inhibin, which acts locally as a tumor suppressor, is down-regulated in tumors and in normal cells during aging. Previous studies suggested that regulation of Inha transcription involves the binding of a protein(s) to a repeat of the GGGGC motif in the promoter. Expression screening identified a cDNA encoding a protein that binds this sequence. Of the RING-H2 family, it is the mouse homologue of a human protein of unknown function, RNF6. The mouse gene, Rnf6, is predominantly expressed in two interacting cell types of the testis, Sertoli cells and pachytene spermatocytes. In Sertoli cells, it colocalizes with the PML and Daxx proteins in punctate nuclear bodies. In transient and stable transfectants, Rnf6 expression from a heterologous promoter increased the expression of reporter genes driven by the Inha promoter. In a Sertoli tumor cell line in which expression of both Inha and Rnf6 was reduced, reexpression of the latter restored the level of Inha while, concomitantly, the cells reverted to normal growth control in culture.
Lopez
Pascal
P
Unité 470 de l'Institut National de la Santé et de la Recherche Médicale, Université de Nice, Nice, France.
Vidal
Frédérique
F
Martin
Luc
L
Lopez-Fernandez
Luis A
LA
Rual
Jean-François
JF
Rosen
Barry S
BS
Cuzin
François
F
Rassoulzadegan
Minoo
M
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007265:Inhibins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012091:Repetitive Sequences, Nucleic Acid; D012708:Sertoli Cells / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D004268:DNA-Binding Proteins; C491473:Daxx protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C119753:RNF6 protein, human; D014157:Transcription Factors; C094377:inhibin-alpha subunit; D007265:Inhibins