title: New molecular bridge between RelA/p65 and NF-κB target genes via histone acetyltransferase TIP60 cofactor.
abstract: The nuclear factor-κB (NF-κB) family is involved in the expressions of numerous genes, in development, apoptosis, inflammatory responses, and oncogenesis. In this study we identified four NF-κB target genes that are modulated by TIP60. We also found that TIP60 interacts with the NF-κB RelA/p65 subunit and increases its transcriptional activity through protein-protein interaction. Although TIP60 binds with RelA/p65 using its histone acetyltransferase domain, TIP60 does not directly acetylate RelA/p65. However, TIP60 maintained acetylated Lys-310 RelA/p65 levels in the TNF-α-dependent NF-κB signaling pathway. In chromatin immunoprecipitation assay, TIP60 was primarily recruited to the IL-6, IL-8, C-IAP1, and XIAP promoters in TNF-α stimulation followed by acetylation of histones H3 and H4. Chromatin remodeling by TIP60 involved the sequential recruitment of acetyl-Lys-310 RelA/p65 to its target gene promoters. Furthermore, we showed that up-regulated TIP60 expression was correlated with acetyl-Lys-310 RelA/p65 expressions in hepatocarcinoma tissues. Taken together these results suggest that TIP60 is involved in the NF-κB pathway through protein interaction with RelA/p65 and that it modulates the transcriptional activity of RelA/p65 in NF-κB-dependent gene expression.
authors.affiliation: From the School of Biological Sciences, Chung-Ang University, Seoul 156-756, South Korea.
authors.forename: Jung-Woong
authors.initials: JW
authors.lastname: Kim
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Jang
authors.forename: Chul-Hong
authors.initials: CH
authors.lastname: Kim
authors.forename: Joo-Hee
authors.initials: JH
authors.lastname: An
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Kang
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Choi
mesh_terms: D000107:Acetylation; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D056945:Hep G2 Cells; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000276:immunology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D000074443:Lysine Acetyltransferase 5; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: C508606:CXCL8 protein, human; D006657:Histones; C508600:IL6 protein, human; D051034:Inhibitor of Apoptosis Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D009363:Neoplasm Proteins; C498143:RELA protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5