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Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP/Collège de France, BP163, 67404 Illkirch-cedex, France
* Present address: Brain Research Institute, University and ETH Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
These authors contributed equally to this work
Authors for correspondence (e-mail: losson{at}titus.u-strasbg.fr and marek{at}titus.u-strasbg.fr)
Accepted 22 February 2002
The gene for transcriptional intermediary factor 1ß (TIF1ß) encodes a transcriptional co-repressor known to play essential roles in chromatin remodeling as well as in early embryonic development. During spermatogenesis, TIF1ß is preferentially associated with heterochromatin structures of Sertoli cells and round spermatids, as well as with meiotic chromosomes. Its expression is tightly regulated within spermatocyte and spermatid populations, and it is undetectable in spermatogonia. Spatiotemporally controlled ablation of TIF1ß by using a germ cell lineage-specific CreERT/loxP system leads to testicular degeneration. This degeneration is not due to impairment of chromatin remodeling processes during meiosis and spermiogenesis, as TIF1ß-deficient spermatocytes are able to complete their differentiation into spermatozoa. It rather occurs as a consequence of shedding of immature germ cells (spermatocytes and spermatids), and disappearance of stem spermatogonia. These results indicate that TIF1ß has important functions in the homeostasis of the seminiferous epithelium, and probably plays a crucial role in the network of paracrine interactions between germ cell subpopulations and/or Sertoli cells.
Key words: Heterochromatin protein 1, Transcriptional silencing, KRAB zinc-finger proteins, Testis-specific conditional knockout, Cellular interactions, Mouse
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