Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA.
Cell. 2011 May 27;145(5):692-706. doi: 10.1016/j.cell.2011.03.053. Epub 2011 May 19.
Little is known about how combinations of histone marks are interpreted at the level of nucleosomes. The second PHD finger of human BPTF is known to specifically recognize histone H3 when methylated on lysine 4 (H3K4me2/3). Here, we examine how additional heterotypic modifications influence BPTF binding. Using peptide surrogates, three acetyllysine ligands are indentified for a PHD-adjacent bromodomain in BPTF via systematic screening and biophysical characterization. Although the bromodomain displays limited discrimination among the three possible acetyllysines at the peptide level, marked selectivity is observed for only one of these sites, H4K16ac, in combination with H3K4me3 at the mononucleosome level. In support, these two histone marks constitute a unique trans-histone modification pattern that unambiguously resides within a single nucleosomal unit in human cells, and this module colocalizes with these marks in the genome. Together, our data call attention to nucleosomal patterning of covalent marks in dictating critical chromatin associations.
关于组蛋白标记如何在核小体水平上被解释，人们知之甚少。已知人类 BPTF 的第二个 PHD 指针对赖氨酸 4 甲基化的组蛋白 H3（H3K4me2/3）具有特异性识别能力。在这里，我们研究了其他异质修饰如何影响 BPTF 的结合。通过系统筛选和生物物理特性分析，使用肽类似物鉴定出 BPTF 中临近 PHD 的溴结构域的三个乙酰赖氨酸配体。尽管溴结构域在肽水平上对三种可能的乙酰赖氨酸显示出有限的区分能力，但在单核小体水平上仅观察到对其中一个位点 H4K16ac 与 H3K4me3 的显著选择性。支持这一观点的是，这两种组蛋白标记构成了一种独特的跨组蛋白修饰模式，在人类细胞中明确位于单个核小体单元内，并且该模块与基因组中的这些标记共定位。总之，我们的数据引起了人们对核小体中共价标记模式在决定关键染色质关联中的作用的关注。
