title: TIF1β association with HP1 is essential for post-gastrulation development, but not for Sertoli cell functions during spermatogenesis.
abstract: TIF1β 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 TIF1β-HP1 interaction, by generating mice in which the TIF1β HP1box is mutated, leading to the loss of TIF1β interaction with HP1. The effects of the mutation were monitored in two instances, where TIF1β is known to play key roles: early embryonic development and spermatogenesis. We find that mutating the HP1box of TIF1β disrupts embryonic development soon after gastrulation. This effect is likely caused by the misexpression of TIF1β targets that regulate mitotic progression and pluripotency. In contrast, in Sertoli cells, we found that the absence of TIF1β 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 TIF1β and HP1 is essential for some but not all TIF1β functions in vivo. Furthermore, we observed that TIF1β 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 TIF1β HP1box mutation. Altogether, these data provide strong evidence that nuclear organization plays key roles during early embryonic development.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch-Cedex, France.
authors.forename: Marielle
authors.initials: M
authors.lastname: Herzog
authors.forename: Olivia
authors.initials: O
authors.lastname: Wendling
authors.forename: Florian
authors.initials: F
authors.lastname: Guillou
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Manuel
authors.initials: M
authors.lastname: Mark
authors.forename: Régine
authors.initials: R
authors.lastname: Losson
authors.forename: Florence
authors.initials: F
authors.lastname: Cammas
mesh_terms: D000818:Animals; D002453:Cell Cycle; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology*; D047108:Embryonic Development; D005260:Female; D054262:Gastrulation; D018398:Homeodomain Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071317:Nanog Homeobox Protein; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D012708:Sertoli Cells / Q000502:physiology*; D013091:Spermatogenesis; D000076183:Tripartite Motif-Containing Protein 28
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D012097:Repressor Proteins; D000090266:Chromobox Protein Homolog 5; C103190:Trim28 protein, mouse; D000076183:Tripartite Motif-Containing Protein 28