Cancer Research UK, London Research Institute, London WC2A 3LY, UK.
EMBO J. 2013 Feb 6;32(3):450-60. doi: 10.1038/emboj.2012.339. Epub 2013 Jan 11.
The TTAGGG motif is common to two seemingly unrelated dimensions of chromatin function-the vertebrate telomere repeat and the promoter regions of many Schizosaccharomyces pombe genes, including all of those encoding canonical histones. The essential S. pombe protein Teb1 contains two Myb-like DNA binding domains related to those found in telomere proteins and binds the human telomere repeat sequence TTAGGG. Here, we analyse Teb1 binding throughout the genome and the consequences of reduced Teb1 function. Chromatin immunoprecipitation (ChIP)-on-chip analysis reveals robust Teb1 binding at many promoters, notably including all of those controlling canonical histone gene expression. A hypomorphic allele, teb1-1, confers reduced binding and reduced levels of histone transcripts. Prompted by previously suggested connections between histone expression and centromere identity, we examined localization of the centromeric histone H3 variant Cnp1 and found reduced centromeric binding along with reduced centromeric silencing. These data identify Teb1 as a master regulator of histone levels and centromere identity.
TTAGGG 基序常见于染色质功能的两个看似不相关的维度-脊椎动物端粒重复序列和许多酿酒酵母裂殖酵母基因的启动子区域,包括编码所有典型组蛋白的基因。必需的酿酒酵母裂殖酵母蛋白 Teb1 包含两个与端粒蛋白中发现的 Myb 样 DNA 结合结构域相关的 Myb 样 DNA 结合结构域,并结合人端粒重复序列 TTAGGG。在这里,我们分析了整个基因组中的 Teb1 结合情况以及 Teb1 功能降低的后果。染色质免疫沉淀(ChIP)-芯片分析显示,在许多启动子上都有强大的 Teb1 结合,特别是包括控制所有典型组蛋白基因表达的启动子。一个功能减弱的等位基因 teb1-1 导致结合减少和组蛋白转录物水平降低。由于先前提出的组蛋白表达与着丝粒身份之间的联系,我们检查了着丝粒组蛋白 H3 变体 Cnp1 的定位,并发现随着着丝粒沉默的减少,着丝粒结合减少。这些数据将 Teb1 鉴定为组蛋白水平和着丝粒身份的主要调节因子。