Role of Jade-1 in the histone acetyltransferase (HAT) HBO1 complex.
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.
Foy
Rebecca L
RL
Department of Medicine, Section of Nephrology, Boston University School of Medicine and Medical Center, Evans Biomedical Research Center, Boston, Massachusetts 02118, USA.
Song
Ihn Young
IY
Chitalia
Vipul C
VC
Cohen
Herbert T
HT
Saksouk
Nehme
N
Cayrou
Christelle
C
Vaziri
Cyrus
C
Côté
Jacques
J
Panchenko
Maria V
MV
D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D051548:Histone Acetyltransferases / Q000378:metabolism / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D020033:Protein Isoforms; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*
D002843:Chromatin; D006657:Histones; D018398:Homeodomain Proteins; C469360:JADE1 protein, human; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D051548:Histone Acetyltransferases; C496553:KAT7 protein, human