Yolande Huss-Garcia | Search PubMed

PubMed2002

Cell differentiation induces TIF1beta association with centromeric heterochromatin via an HP1 interaction.

The transcriptional intermediary factor 1 (TIF1) family protein TIF1beta is a corepressor for Krüppel-associated box (KRAB)-domain-containing zinc finger proteins and plays a critical role in early embryogenesis. Here, we examined TIF1beta 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 TIF1beta 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 TIF1beta, 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 TIF1beta that is regulated during cell differentiation through a mechanism that requires HP1 interaction.

Amino Acid Sequence↗

PubMed2002

E2Fs regulate adipocyte differentiation.

When preadipocytes reenter the cell cycle, PPAR gamma expression is induced, coincident with an increase in DNA synthesis, suggesting the involvement of the E2F family of cell cycle regulators. We show here that E2F1 induces PPAR gamma transcription during clonal expansion, whereas E2F4 represses PPARg amma expression during terminal adipocyte differentiation. Using a combination of in vivo experiments with knockout and chimeric animals and in vitro experiments, we demonstrate that the absence of E2F1 impairs, whereas depletion of E2F4 stimulates, adipogenesis. E2Fs hence represent the link between proliferative signaling pathways, triggering clonal expansion, and terminal adipocyte differentiation through regulation of PPAR gamma expression. This underscores the complex role of the E2F protein family in the control of both cell proliferation and differentiation.

3T3 Cells↗