Department of Biochemistry & Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Sci Rep. 2012;2:489. doi: 10.1038/srep00489. Epub 2012 Jul 3.
Antibodies specific for histone post-translational modifications (PTMs) have been central to our understanding of chromatin biology. Here, we describe an unexpected and novel property of histone H4 site-specific acetyl antibodies in that they prefer poly-acetylated histone substrates. By all current criteria, these antibodies have passed specificity standards. However, we find these site-specific histone antibodies preferentially recognize chromatin signatures containing two or more adjacent acetylated lysines. Significantly, we find that the poly-acetylated epitopes these antibodies prefer are evolutionarily conserved and are present at levels that compete for these antibodies over the intended individual acetylation sites. This alarming property of acetyl-specific antibodies has far-reaching implications for data interpretation and may present a challenge for the future study of acetylated histone and non-histone proteins.
针对组蛋白翻译后修饰（PTMs）的抗体一直是我们理解染色质生物学的核心。在这里，我们描述了组蛋白 H4 特异性乙酰化抗体的一个意外的新特性，即它们偏爱多乙酰化组蛋白底物。根据所有现行标准，这些抗体都通过了特异性标准。然而，我们发现这些组蛋白特异性抗体优先识别含有两个或更多相邻乙酰化赖氨酸的染色质特征。重要的是，我们发现这些抗体偏好的多乙酰化表位在进化上是保守的，并且存在的水平足以与预期的单个乙酰化位点竞争这些抗体。这种乙酰特异性抗体的惊人特性对数据解释具有深远的影响，并且可能对乙酰化组蛋白和非组蛋白的未来研究提出挑战。
