Role of Jade-1 in the Histone Acetyltransferase (HAT) HBO1 Complex

被引:58
作者
Foy, Rebecca L. [2 ]
song, Ihn Young [1 ,3 ]
Chitalia, Vipul C. [2 ]
Cohen, Herbert T. [2 ]
Saksouk, Nehme [4 ]
Cayrou, Christelle [4 ]
Vaziri, Cyrus [1 ,3 ]
Cote, Jacques [4 ]
Panchenko, Maria V. [1 ,2 ,3 ]
机构
[1] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Dept Med, Nephrol Sect, Boston, MA 02118 USA
[3] Evans Biomed Res Ctr, Med Ctr, Boston, MA 02118 USA
[4] Univ Laval, Canc Res Ctr, Hotel Dieu Quebec, CHU Quebec, Quebec City, PQ G1R 2J6, Canada
关键词
D O I
10.1074/jbc.M801407200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Regulation of global chromatin acetylation is important for chromatin remodeling. A small family of Jade proteins includes Jade-1L, Jade-2, and Jade-3, each bearing two mid-molecule tandem plant homology domain (PHD) zinc fingers. We previously demonstrated that the short isoform of Jade-1L protein, Jade-1, is associated with endogenous histone acetyltransferase (HAT) activity. It has been found that Jade-1L/2/3 proteins co-purify with a novel HAT complex, consisting of HBO1, ING4/5, and Eaf6. We investigated a role for Jade-1/1L in the HBO1 complex. When overexpressed individually, neither Jade-1/1L nor HBO1 affected histone acetylation. However, co-expression of Jade1/1L and HBO1 increased acetylation of the bulk of endogenous histone H4 in epithelial cells in a synergistic manner, suggesting that Jade1/1L positively regulates HBO1 HAT activity. Conversely, small interfering RNA-mediated depletion of endogenous Jade resulted in reduced levels of H4 acetylation. Moreover, HBO1-mediated H4 acetylation activity was enhanced severalfold by the presence of Jade-1/1L in vitro. The removal of PHD fingers affected neither binding nor mutual Jade-1-HBO1 stabilization but completely abrogated the synergistic Jade-1/1L- and HBO1-mediated histone H4 acetylation in live cells and in vitro with reconstituted oligonucleosome substrates. Therefore, PHDs are necessary for Jade-1/1L- induced acetylation of nucleosomal histones by HBO1. In contrast to Jade-1/1L, the PHD zinc finger protein ING4/5 failed to synergize with HBO1 to promote histone acetylation. The physical interaction of ING4/5 with HBO1 occurred in the presence of Jade-1L or Jade-3 but not with the Jade-1 short isoform. In summary, this study demonstrates that Jade-1/1L are crucial co-factors for HBO1-mediated histone H4 acetylation.
引用
收藏
页码:28817 / 28826
页数:10
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