Sims Jennifer K, Houston Sabrina I, Magazinnik Tanya, Rice Judd C
Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA.
J Biol Chem. 2006 May 5;281(18):12760-6. doi: 10.1074/jbc.M513462200. Epub 2006 Mar 3.
The specific post-translational modifications of the histone proteins are associated with specific DNA-templated processes, such as transcriptional activation or repression. To investigate the biological role(s) of histone H4 lysine 20 (H4 Lys-20) methylation, we created a novel panel of antibodies that specifically detected mono-, di-, or trimethylated H4 Lys-20. We report that the different methylated forms of H4 Lys-20 are compartmentalized within visually distinct, transcriptionally silent regions in the mammalian nucleus. Interestingly, direct comparison of methylated H4 Lys-20 with the different methylated states of histone H3 lysine 9 (H3 Lys-9) revealed significant overlap and exclusion between the specific groups of methyl modifications. Trimethylated H4 Lys-20 and H3 Lys-9 were both selectively enriched within pericentric heterochromatin. Similarly, monomethylated H4 Lys-20 and H3 Lys-9 partitioned together and the dimethylated forms partitioned together within the chromosome arms; however, the mono- and dimethylated modifications were virtually exclusive. These findings strongly suggest that the combinatorial presence or absence of the different methylated states of H4 Lys-20 and H3 Lys-9 define particular types of silent chromatin. Consistent with this, detailed analysis of monomethylated H4 Lys-20 and H3 Lys-9 revealed that both were preferentially and selectively enriched within the same nucleosome particle in vivo. Collectively, these findings define a novel trans-tail histone code involving monomethylated H4 Lys-20 and H3 Lys-9 that act cooperatively to mark distinct regions of silent chromatin within the mammalian epigenome.
组蛋白的特定翻译后修饰与特定的DNA模板化过程相关，如转录激活或抑制。为了研究组蛋白H4赖氨酸20（H4 Lys-20）甲基化的生物学作用，我们创建了一组新型抗体，可特异性检测单甲基化、二甲基化或三甲基化的H4 Lys-20。我们报告称，H4 Lys-20的不同甲基化形式在哺乳动物细胞核中视觉上不同的转录沉默区域内进行分隔。有趣的是，将甲基化的H4 Lys-20与组蛋白H3赖氨酸9（H3 Lys-9）的不同甲基化状态进行直接比较，发现特定甲基修饰组之间存在显著的重叠和排斥。三甲基化的H4 Lys-20和H3 Lys-9都选择性地富集在着丝粒周围的异染色质中。同样，单甲基化的H4 Lys-20和H3 Lys-9一起分布，二甲基化形式在染色体臂内一起分布；然而，单甲基化和二甲基化修饰实际上是相互排斥的。这些发现强烈表明，H4 Lys-20和H3 Lys-9不同甲基化状态的组合存在或不存在定义了特定类型的沉默染色质。与此一致的是，对单甲基化的H4 Lys-20和H3 Lys-9的详细分析表明，两者在体内均优先且选择性地富集在同一核小体颗粒中。总的来说，这些发现定义了一种新的跨尾部组蛋白密码，涉及单甲基化的H4 Lys-20和H3 Lys-9，它们协同作用以标记哺乳动物表观基因组内沉默染色质的不同区域。
