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Publication : A Suv39h-dependent mechanism for silencing S-phase genes in differentiating but not in cycling cells.

First Author  Ait-Si-Ali S Year  2004
Journal  EMBO J Volume  23
Issue  3 Pages  605-15
PubMed ID  14765126 Mgi Jnum  J:88283
Mgi Id  MGI:3032473 Doi  10.1038/sj.emboj.7600074
Citation  Ait-Si-Ali S, et al. (2004) A Suv39h-dependent mechanism for silencing S-phase genes in differentiating but not in cycling cells. EMBO J 23(3):605-15
abstractText  The Rb/E2F complex represses S-phase genes both in cycling cells and in cells that have permanently exited from the cell cycle and entered a terminal differentiation pathway. Here we show that S-phase gene repression, which involves histone-modifying enzymes, occurs through distinct mechanisms in these two situations. We used chromatin immunoprecipitation to show that methylation of histone H3 lysine 9 (H3K9) occurs at several Rb/E2F target promoters in differentiating cells but not in cycling cells. Furthermore, phenotypic knock-down experiments using siRNAs showed that the histone methyltransferase Suv39h is required for histone H3K9 methylation and subsequent repression of S-phase gene promoters in differentiating cells, but not in cycling cells. These results indicate that the E2F target gene permanent silencing mechanism that is triggered upon terminal differentiation is distinct from the transient repression mechanism in cycling cells. Finally, Suv39h-depleted myoblasts were unable to express early or late muscle differentiation markers. Thus, appropriately timed H3K9 methylation by Suv39h seems to be part of the control switch for exiting the cell cycle and entering differentiation.
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