%0 Journal Article
%T Phosphorylation at Ser473 regulates heterochromatin protein 1 binding and corepressor function of TIF1beta/KAP1
%A Chiung-Wen Chang
%A Han-Yi Chou
%A Yu-Sheng Lin
%A Kuo-Hsiang Huang
%A Ching-Jin Chang
%A Tsui-Chun Hsu
%A Sheng-Chung Lee
%J BMC Molecular Biology
%D 2008
%I BioMed Central
%R 10.1186/1471-2199-9-61
%X This work demonstrates that TIF1¦Â is phosphorylated on Ser473, the alteration of which is dynamically associated with cell cycle progression and functionally linked to transcriptional regulation. Phosphorylation of TIF1¦Â/Ser473 coincides with the induction of cell cycle gene cyclin A2 at the S-phase. Interestingly, chromatin immunoprecipitation demonstrated that the promoter of cyclin A2 gene is occupied by TIF1¦Â and that such occupancy is inversely correlated with Ser473 phosphorylation. Additionally, when HP1¦Â was co-expressed with TIF1¦Â/S473A, but not TIF1¦Â/S473E, the colocalization of TIF1¦Â/S473A and HP1¦Â to the promoters of Cdc2 and Cdc25A was enhanced. Non-phosphorylated TIF1¦Â/Ser473 allowed greater TIF1¦Â association with the regulatory regions and the consequent repression of these genes. Consistent with possible inhibition of TIF1¦Â's corepressor function, the phosphorylation of the Ser473 residue, which is located near the HP1-interacting PXVXL motif, compromised the formation of TIF1¦Â-HP1 complex. Finally, we found that the phosphorylation of TIF1¦Â/Ser473 is mediated by the PKC¦Ä pathway and is closely linked to cell proliferation.The modulation of HP1¦Â-TIF1¦Â interaction through the phosphorylation/de-phosphorylation of TIF1¦Â/Ser473 may constitute a molecular switch that regulates the expression of particular genes. Higher levels of phosphorylated TIF1¦Â/Ser473 may be associated with the expression of key regulatory genes for cell cycle progression and the proliferation of cells.Transcriptional intermediary factor TIF1¦Â and heterochromatin protein 1 profoundly impact the regulation of the structure and function of chromatin [1]. The heterochromatin protein 1 (HP1) family of proteins (HP1¦Á, HP1¦Â, and HP1¦Ã) participates in gene silencing by forming heterochromatic structures [2,3]. HP1 exhibits distinct nuclear localization patterns: HP1¦Á nassociates with centromeres while HP1¦Â and HP1¦Ã are largely localized in distinct nuclear regions. The nuclear arrangement
%U http://www.biomedcentral.com/1471-2199/9/61