Adolf-Butenandt-Institute, Department of Molecular Biology, Ludwig Maximilians University of Munich, 80336 Munich, Germany.
J Cell Biol. 2010 Sep 6;190(5):777-91. doi: 10.1083/jcb.201002043.
Nucleosomal incorporation of specialized histone variants is an important mechanism to generate different functional chromatin states. Here, we describe the identification and characterization of two novel primate-specific histone H3 variants, H3.X and H3.Y. Their messenger RNAs are found in certain human cell lines, in addition to several normal and malignant human tissues. In keeping with their primate specificity, H3.X and H3.Y are detected in different brain regions. Transgenic H3.X and H3.Y proteins are stably incorporated into chromatin in a similar fashion to the known H3 variants. Importantly, we demonstrate biochemically and by mass spectrometry that endogenous H3.Y protein exists in vivo, and that stress stimuli, such as starvation and cellular density, increase the abundance of H3.Y-expressing cells. Global transcriptome analysis revealed that knockdown of H3.Y affects cell growth and leads to changes in the expression of many genes involved in cell cycle control. Thus, H3.Y is a novel histone variant involved in the regulation of cellular responses to outside stimuli.
核小体中特殊组蛋白变体的掺入是产生不同功能染色质状态的重要机制。在这里,我们描述了两种新型灵长类特异性组蛋白 H3 变体 H3.X 和 H3.Y 的鉴定和表征。它们的信使 RNA 不仅存在于某些人类细胞系中,还存在于几种正常和恶性的人类组织中。与它们的灵长类特异性一致,H3.X 和 H3.Y 存在于不同的脑区。转染的 H3.X 和 H3.Y 蛋白以类似于已知 H3 变体的方式稳定地掺入染色质中。重要的是,我们通过生化和质谱分析证明了内源性 H3.Y 蛋白在体内的存在,并且应激刺激,如饥饿和细胞密度增加了表达 H3.Y 的细胞的丰度。全转录组分析显示,H3.Y 的敲低会影响细胞生长,并导致参与细胞周期调控的许多基因的表达发生变化。因此,H3.Y 是一种新型的组蛋白变体,参与细胞对外界刺激的反应的调控。