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Translocation of forkhead box O1 to the nuclear periphery induces histone modifications that regulate transcriptional repression of PCK 1 in HepG2 cells
Author(s) -
Arai Tamaki,
Kano Fumi,
Murata Masayuki
Publication year - 2015
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12226
Subject(s) - biology , forkhead transcription factors , psychological repression , histone , transcription factor , foxo1 , microbiology and biotechnology , foxo3 , phosphorylation , gene expression , gene , protein kinase b , genetics
Forkhead box O1 ( FOXO 1) is an important target for insulin. It is widely accepted that insulin‐induced phosphorylation of FOXO 1 by Akt leads to its nuclear exclusion and results in the inhibition of FOXO 1‐mediated transcription of the gluconeogenic gene phosphoenolpyruvate carboxykinase 1 ( PCK 1 ) in hepatocytes. However, many results that contradict this model have accumulated. Here, we provide a new mechanism for insulin‐dependent repression of FOXO 1‐mediated transcription. We showed insulin‐induced translocation of endogenous Ser256‐phosphorylated FOXO 1, which is essential for regulation of FOXO 1‐mediated transcription, from nuclear speckles to the nuclear periphery. This insulin‐dependent translocation of FOXO 1 regulated transcriptional repression of PCK 1 concomitant with the formation of the FOXO 1‐euchromatic histone‐lysine N‐methyltransferase2 ( EHMT 2) complex and histone modifications of the PCK 1 promoter region. Notably, our results suggest that FOXO 1 uses nucleoporin 98 kDa NUP 98 for this transcriptional regulation. These results provide a new insight into various FOXO 1‐mediated transcriptional regulation and FOXO 1‐mediated essential biological pathways.