p65 赖氨酸 314 乙酰化对于晚期 NF-κB 依赖基因表达很重要。

Acetylation of p65 at lysine 314 is important for late NF-kappaB-dependent gene expression.

机构信息

Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.

出版信息

BMC Genomics. 2010 Jan 11;11:22. doi: 10.1186/1471-2164-11-22.

BACKGROUND

NF-kappaB regulates the expression of a large number of target genes involved in the immune and inflammatory response, apoptosis, cell proliferation, differentiation and survival. We have earlier reported that p65, a subunit of NF-kappaB, is acetylated in vitro and in vivo at three different lysines (K310, K314 and K315) by the histone acetyltransferase p300.

RESULTS

In this study, we describe that site-specific mutation of p65 at lysines 314 and 315 enhances gene expression of a subset of NF-kappaB target genes including Mmp10 and Mmp13. Increased gene expression was mainly observed three hours after TNFalpha stimulation. Chromatin immunoprecipitation (ChIP) experiments with an antibody raised against acetylated lysine 314 revealed that chromatin-bound p65 is indeed acetylated at lysine 314.

CONCLUSIONS

Together, our results establish acetylation of K314 as an important regulatory modification of p65 and subsequently of NF-kappaB-dependent gene expression.

背景

NF-κB 调节着大量与免疫和炎症反应、细胞凋亡、细胞增殖、分化和存活相关的靶基因的表达。我们之前的研究报告表明，NF-κB 的一个亚基 p65 在体外和体内可被组蛋白乙酰转移酶 p300 乙酰化于三个不同的赖氨酸（K310、K314 和 K315）上。

结果

在这项研究中，我们描述了 p65 赖氨酸 314 和 315 的定点突变增强了包括 MMP10 和 MMP13 在内的一组 NF-κB 靶基因的基因表达。在 TNFα 刺激后三小时主要观察到基因表达增加。针对赖氨酸 314 乙酰化的抗体进行的染色质免疫沉淀（ChIP）实验表明，染色质结合的 p65 确实在赖氨酸 314 处被乙酰化。