Premium
The transcription factor ZBP‐89 suppresses p16 expression through a histone modification mechanism to affect cell senescence
Author(s) -
Feng Yunpeng,
Wang Xiuli,
Xu Liang,
Pan Hong,
Zhu Shan,
Liang Qian,
Huang Baiqu,
Lu Jun
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07128.x
Subject(s) - chromatin immunoprecipitation , biology , immunoprecipitation , acetylation , microbiology and biotechnology , transcription factor , gene knockdown , senescence , rna interference , hdac4 , histone , histone deacetylase , gene expression , biochemistry , apoptosis , rna , promoter , cell culture , genetics , gene
The transcription factor ZBP‐89 has been implicated in the induction of growth arrest and apoptosis. In this article, we demonstrate that ZBP‐89 was able to restrain senescence in NCI‐H460 human lung cancer cells, through epigenetically regulating p16 INK4a expression. Specifically, our results indicate that knockdown of ZBP‐89 by RNA interference stimulated cellular senescence in NCI‐H460 cells, as judged by the senescence‐associated β‐galactosidase activity assay and senescence‐associated heterochromatin foci assay, and this process could be reversed by RNA interference‐mediated p16 INK4a silencing. We also show that histone deacetylase (HDAC) 3 and HDAC4 inhibited p16 INK4a promoter activity in a dose‐dependent manner. Furthermore, chromatin immunoprecipitation assays verified that HDAC3 was recruited to the p16 INK4a promoter by ZBP‐89 through an epigenetic mechanism involving histone acetylation modification. Moreover, immunofluorescence and coimmunoprecipitation assays revealed that ZBP‐89 and HDAC3 formed a complex. These data suggest that ZBP‐89 and HDAC3, but not HDAC4, can work coordinately to restrain cell senescence by downregulating p16 INK4a expression through an epigenetic modification of histones. Structured digital abstract• MINT‐7144512 : HDAC4 (uniprotkb: P56524 ) physically interacts ( MI:0914 ) with ZBP‐89 (uniprotkb: Q9UQR1 ) by anti tag coimmunoprecipitation ( MI:0007 ) • MINT‐7144482 , MINT‐7144499 : ZBP‐89 (uniprotkb: Q9UQR1 ) physically interacts ( MI:0914 ) with HDAC3 (uniprotkb: O15379 ) by anti tag coimmunoprecipitation ( MI:0007 ) • MINT‐7144469 : ZBP‐89 (uniprotkb: Q9UQR1 ) and HDAC3 (uniprotkb: O15379 ) colocalize ( MI:0403 ) by fluorescence microscopy ( MI:0416 )