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TIF1γ, a novel member of the transcriptional intermediary factor 1 family

Abstract

We report the cloning and characterization of a novel member of the Transcriptional Intermediary Factor 1 (TIF1) gene family, human TIF1γ. Similar to TIF1α and TIF1β, the structure of TIF1β is characterized by multiple domains: RING finger, B boxes, Coiled coil, PHD/TTC, and bromodomain. Although structurally related to TIF1α and TIF1β, TIF1γ presents several functional differences. In contrast to TIF1α, but like TIF1β, TIF1γ does not interact with nuclear receptors in yeast two-hybrid or GST pull-down assays and does not interfere with retinoic acid response in transfected mammalian cells. Whereas TIF1α and TIF1β were previously found to interact with the KRAB silencing domain of KOX1 and with the HP1α, MOD1 (HP1β) and MOD2 (HP1γ) heterochromatinic proteins, suggesting that they may participate in a complex involved in heterochromatin-induced gene repression, TIF1γ does not interact with either the KRAB domain of KOX1 or the HP1 proteins. Nevertheless, TIF1γ, like TIF1α and TIF1β, exhibits a strong silencing activity when tethered to a promoter. Since deletion of a novel motif unique to the three TIF1 proteins, called TIF1 signature sequence (TSS), abrogates transcriptional repression by TIF1γ, this motif likely participates in TIF1 dependent repression.

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Acknowledgements

We are grateful to T Miki and SA Aaronson for their generous gift of T18 cDNA. We acknowledge B Grabow and M Cerviño for technical assistance, S Vicaire for control sequencing of plasmid constructs, and F Ruffenach and A Staub for oligonucleotide synthesis. We thank our colleagues at UPR 9051 CNRS, IGBMC, and MHH for discussions and critical reading of the manuscript, and B Lüscher for helpful suggestions. This work was supported by the Centre National de la Recherche Scientifique, the Institut National de la Santé et de la Recherche Médicale, the Ligue contre le Cancer, the Fondation de France, the Fondation St. Louis, the Association pour la Recherche sur le Cancer, the Groupement de Recherches et d'Etudes sur les Génomes (GREG 47/95), the Centre Hospitalier Universitaire Régional, the Collège de France, and the Deutsche Forschungsgemeinschaft (Sta 374/2-1). Genbank/EMBL accession Nos.: AF119042 (hTIF1α, AF11904 (hTIF1γ).

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Venturini, L., You, J., Stadler, M. et al. TIF1γ, a novel member of the transcriptional intermediary factor 1 family. Oncogene 18, 1209–1217 (1999). https://doi.org/10.1038/sj.onc.1202655

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