The Functional Analysis of TIF1beta on the Regulation of Cell Cycle
Date Issued
2008
Date
2008
Author(s)
Lin, Yu-Sheng
Abstract
The transcriptional intermediary factor 1β (TIF1β)/KRIP-1/KAP-1/TRIM28 is an epigenetic regulator correlated to transcriptional regulation and chromatin remodeling at designated genomic loci through the interaction with other chromatinic proteins. The repressive capability of TIF1β is thought to be mediated in part by its interaction with HP1. The HP1-box, PXVXL, of TIF1β is reported to be responsible for this interaction.owever, the underlying regulation is still poorly understood. Here we demonstrate the construction of a gene replacement system which replaces the endogenous TIF1β withctopically expressed ones carrying desired alterations. Also, using phospho-specific antibody, it is shown that TIF1β is phosphorylated at Ser473, which is located in theP1-interacting domain, and the global level of this modification fluctuates with the progression of cell cycle. Furthermore, in our ChIP assay, it is shown that theverexpression of wild type and S473A but not the phospho-mimicry S473E mutant of TIF1β can preferentially enrich the recruitment of HP1β to endogenous promoter region of CDC2 and CDC25a. In conclusion, the phosphorylation of TIF1β Ser473 is demonstrated to be functionally correlated to the recruitment of HP1 protein to specific chromatinic loci. Finally, we’ve also provided the evidence that TIF1β can potentially complex with the histone acetyltransferases PCAF, and this interaction is possibly involved in the TIF1β-mediated transcriptional activation reported previously.
Subjects
TIF1beta
HP-1
Epigenetics
Phosphorylation
Transcriptional Regulation
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