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Journal of Cell Science 115, 3439-3448 (2002)
© 2002 The Company of Biologists Limited

Research Article

Cell differentiation induces TIF1ß association with centromeric heterochromatin via an HP1 interaction

Florence Cammas, Mustapha Oulad-Abdelghani, Jean-Luc Vonesch, Yolande Huss-Garcia, Pierre Chambon* and Régine Losson

Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP/Collège de France, BP163, 67404 Illkirch-Cedex, France

* Author for correspondence (e-mail: chambon{at}igbmc.u-strasbg.fr)

Accepted 12 June 2002

The transcriptional intermediary factor 1 (TIF1) family protein TIF1ß is a corepressor for Krüppel-associated box (KRAB)-domain-containing zinc finger proteins and plays a critical role in early embryogenesis. Here, we examined TIF1ß distribution in the nucleus of mouse embryonic carcinoma F9 cells during retinoic-acid-induced primitive endodermal differentiation. Using confocal immunofluorescence microscopy, we show that, although TIF1ß is diffusely distributed throughout the nucleoplasm of undifferentiated cells, it relocates and concentrates into distinct foci of centromeric heterochromatin in differentiated cells characterized by a low proliferation rate and a well developed cytokeratin network. This relocation was not observed in isoleucine-deprived cells, which are growth arrested, or in compound RXR{alpha}-/-/RAR{gamma}-/- null mutant cells, which are resistant to RA-induced differentiation. Amino-acid substitutions in the PxVxL motif of TIF1ß, which abolish interaction with members of the heterochromatin protein 1 (HP1) family, prevent its centromeric localization in differentiated cells. Collectively, these data provide compelling evidence for a dynamic nuclear compartmentalization of TIF1ß that is regulated during cell differentiation through a mechanism that requires HP1 interaction.

Key words: Nuclear compartmentalization, Transcriptional silencing, Endodermal differentiation, Transcriptional intermediary factor 1 ß, Heterochromatin protein 1


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