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Heterochromatin protein 1 (HP1) proteins are fundamental units of heterochromatin packaging.In mammals, there are three HP1 homologues termed HP1α(Cbx5), HP1β(Cbx1) and HP1γ(Cbx3).HP1β is the best characterized isoform.Murine HP1β is essential for organismal survival.This study demonstrates that Cbx1+/- and Cbx1-/- MEFs escape senescence crisis that is associated with chromosomal aberrations.Telomeres of late passage Cbx1-/- MEFs are longer than WT controls. Introduction of Cbx1-/- mutation in cells expressing H-rasV12 oncogene did not result senescence bypass.K-rasV12 oncogene expression in Cbx1+/- mice resulted in increased malignant adenocarcinomas.These data indicate that HP1β acts as a tumour suppressor.Other experiments showed that binding of HP1β to histone H3(HH3) is resistant to high salt concentrations.ITC experiments confirmed that binding affinity of HP1β for HH3 was 4 times higher than for H3K9me3.The high affinity binding of HP1β to the HH3 is shown to be stronger than the affinity to H3K9me3.Loss of this interaction might result in the perinatal lethal phenotype seen in Cbx1-/- mice.

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9783838123196

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