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Research Article |
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
-/-/RAR
-/- 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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