title: The chromodomain-containing histone acetyltransferase TIP60 acts as a code reader, recognizing the epigenetic codes for initiating transcription.
abstract: TIP60 can act as a transcriptional activator or a repressor depending on the cellular context. However, little is known about the role of the chromodomain in the functional regulation of TIP60. In this study, we found that TIP60 interacted with H3K4me3 in response to TNF-α signaling. TIP60 bound to H3K4me3 at the promoters of the NF-κB target genes IL6 and IL8. Unlike the wild-type protein, a TIP60 chromodomain mutant did not localize to chromatin regions. Because TIP60 binds to histones with specific modifications and transcriptional regulators, we used a histone peptide assay to identify histone codes recognized by TIP60. TIP60 preferentially interacted with methylated or acetylated histone H3 and H4 peptides. Phosphorylation near a lysine residue significantly reduced the affinity of TIP60 for the modified histone peptides. Our findings suggest that TIP60 acts as a functional link between the histone code and transcriptional regulators.
authors.affiliation: a Department of Life Science, College of Natural Sciences , Chung-Ang University , Seoul , Korea.
authors.forename: Chul-Hong
authors.initials: CH
authors.lastname: Kim
authors.forename: Jung-Woong
authors.initials: JW
authors.lastname: Kim
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Jang
authors.forename: Joo-Hee
authors.initials: JH
authors.lastname: An
authors.forename: Sang-Beom
authors.initials: SB
authors.lastname: Seo
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Choi
mesh_terms: D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005815:Genetic Code; D056945:Hep G2 Cells; D051548:Histone Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D000074443:Lysine Acetyltransferase 5; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D040081:Protein Array Analysis; D011485:Protein Binding / Q000187:drug effects; D025941:Protein Interaction Mapping; D015398:Signal Transduction; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D002843:Chromatin; D006657:Histones; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5
keywords: TIP60; chromodomain; code reader; histone modification; transcriptional regulation