TIF1beta association with HP1 is essential for post-gastrulation development, but not for Sertoli cell functions during spermatogenesis.
Fiche publication
Date publication
février 2011
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
Tous les auteurs :
Herzog M, Wendling O, Guillou F, Chambon P, Mark M, Losson R, Cammas F
Lien Pubmed
Résumé
TIF1beta is an essential mammalian transcriptional corepressor. It interacts with the heterochromatin proteins HP1 through a highly conserved motif, the HP1box, and we have previously shown that this interaction is essential for the differentiation of F9 cells to occur. Here we address the in vivo functions of the TIF1beta-HP1 interaction, by generating mice in which the TIF1beta HP1box is mutated, leading to the loss of TIF1beta interaction with HP1. The effects of the mutation were monitored in two instances, where TIF1beta is known to play key roles: early embryonic development and spermatogenesis. We find that mutating the HP1box of TIF1beta disrupts embryonic development soon after gastrulation. This effect is likely caused by the misexpression of TIF1beta targets that regulate mitotic progression and pluripotency. In contrast, in Sertoli cells, we found that the absence of TIF1beta but not its mutation in the HP1box leads to a clear defect of spermatogenesis characterized by a failure of spermatid release and a testicular degeneration. These data show that the interaction between TIF1beta and HP1 is essential for some but not all TIF1beta functions in vivo. Furthermore, we observed that TIF1beta is dispersed through the nucleoplasm of E7.0 embryos, whereas it is mainly associated with pericentromeric heterochromatin of E8.5 embryos and of Sertoli cells, an association that is lost upon TIF1beta HP1box mutation. Altogether, these data provide strong evidence that nuclear organization plays key roles during early embryonic development.
Référence
Dev Biol. 2011 Feb 15;350(2):548-58