Kim Chul-Hong, Kim Jung-Woong, Jang Sang-Min, An Joo-Hee, Seo Sang-Beom, Choi Kyung-Hee
a Department of Life Science, College of Natural Sciences , Chung-Ang University , Seoul , Korea.
Biosci Biotechnol Biochem. 2015;79(4):532-8. doi: 10.1080/09168451.2014.993914. Epub 2015 Jan 3.
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.
TIP60可根据细胞环境充当转录激活因子或抑制因子。然而，关于染色质结构域在TIP60功能调节中的作用知之甚少。在本研究中，我们发现TIP60响应TNF-α信号与H3K4me3相互作用。TIP60与NF-κB靶基因IL6和IL8启动子处的H3K4me3结合。与野生型蛋白不同，TIP60染色质结构域突变体不定位到染色质区域。由于TIP60与具有特定修饰的组蛋白和转录调节因子结合，我们使用组蛋白肽分析来鉴定TIP60识别的组蛋白密码。TIP60优先与甲基化或乙酰化的组蛋白H3和H4肽相互作用。赖氨酸残基附近的磷酸化显著降低了TIP60对修饰组蛋白肽的亲和力。我们的研究结果表明，TIP60充当组蛋白密码和转录调节因子之间的功能联系。
