Abstract
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 Jade-1/1L 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.
Highlights
Gene for apoptosis and differentiation-1, Jade-1 (PHF17), has been identified as a protein interacting with the von Hippel
It has been shown that stable ING4 and ING5 complexes copurify with endogenous Jade-1L/2/3 and HBO1 proteins [7]
To address the possible role of Jade-1 in regulating HBO1 function, we examined the effects of Jade-1 expression levels on HBO1dependent acetylation of endogenous histone H4 in intact cells
Summary
Gene for apoptosis and differentiation-1, Jade-1 (PHF17), has been identified as a protein interacting with the von Hippel. The histone H4-specific HAT, TIP60, interacted with Jade-1 physically and functionally in vitro and in live cells. In contrast to Jade-1L, the truncated version of Jade-1 was not found within the native HBO1 complex or any HAT complexes. These studies identified HAT HBO1 as a native Jade-1L partner and supported Jade-1 association with endogenous histone H4-specific HAT [4]. HBO1 (MYST2, KAT7 [8]) was originally identified using a yeast two-hybrid screen as an origin recognition complex-1 (Orc1)-interacting HAT [9, 10].
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