Transcription and Disease Laboratory, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore-560064, India.
J Biochem. 2012 Nov;152(5):453-62. doi: 10.1093/jb/mvs093. Epub 2012 Aug 25.
Histone modifications; acetylation, methylation (both Lysine and Arginine) etc., at different positions regulates the chromatin fluidity and function in a combinatorial manner, which could be referred as an epigenetic language. In the context of transcription, histone acetylation, methylation and phosphorylation at specific sites, especially at the N-terminal tails of histones play very important roles in activation and/or repression. While acetylation of histones is generally important for transcriptional activation, methylation and phosphorylation could also be involved in repression, depending on the context. Here, we have investigated the crosstalk of histone modifications on a gross scale over histone H3, using a small molecule inhibitor of lysine acetyltransferase KAT3B/p300, Plumbagin, to analyze the histone modification profile upon inhibition of acetylation. In addition to the inhibition of acetylation, there was a concomitant decrease of transcriptional activation mark, H3 lysine 4 trimethylation (H3K4me3) in the cellular context. The histone H3 Serine 10 Phosphorylation (H3S10p) also decreased upon inhibition of acetylation. However, there were no changes observed with transcriptional repressive marks like H3 Lysine 9 di/trimethylation (H3K9me2/me3) suggesting that transcriptional activation marks were selectively targeted. These data suggest that Plumbagin induces a distinct modification profile involving transcriptional activation marks H3K4me3 and H3S10 phosphorylation in the context of histone acetylation brought about by KAT3B/ p300.
组蛋白修饰；乙酰化、甲基化（赖氨酸和精氨酸）等，在不同位置以组合方式调节染色质的流动性和功能，这可以被称为表观遗传语言。在转录的背景下，组蛋白在特定位置（尤其是组蛋白 N 端尾部）的乙酰化、甲基化和磷酸化在激活和/或抑制中起着非常重要的作用。虽然组蛋白的乙酰化通常对转录激活很重要，但甲基化和磷酸化也可能参与抑制，这取决于具体情况。在这里，我们使用赖氨酸乙酰转移酶 KAT3B/p300 的小分子抑制剂 Plumbagin ，在组蛋白 H3 上大规模研究了组蛋白修饰之间的串扰，以分析抑制乙酰化后组蛋白修饰的图谱。除了抑制乙酰化外，在细胞环境中还伴随着转录激活标记物组蛋白 H3 赖氨酸 4 三甲基化（H3K4me3）的减少。组蛋白 H3 丝氨酸 10 磷酸化（H3S10p）在抑制乙酰化后也减少。然而，对于转录抑制标记物，如组蛋白 H3 赖氨酸 9 二甲基/三甲基化（H3K9me2/me3），没有观察到变化，这表明转录激活标记物是选择性靶向的。这些数据表明，Plumbagin 在 KAT3B/p300 引起的组蛋白乙酰化的背景下，诱导了一种涉及转录激活标记物 H3K4me3 和 H3S10 磷酸化的独特修饰谱。
