Ju Bong-Gun, Lunyak Victoria V, Perissi Valentina, Garcia-Bassets Ivan, Rose David W, Glass Christopher K, Rosenfeld Michael G
Howard Hughes Medical Institute, Department of Medicine, School of Medicine, 9500 Gilman Drive, University of California, San Diego, La Jolla, CA 92093-0648, USA.
Science. 2006 Jun 23;312(5781):1798-802. doi: 10.1126/science.1127196.
Multiple enzymatic activities are required for transcriptional initiation. The enzyme DNA topoisomerase II associates with gene promoter regions and can generate breaks in double-stranded DNA (dsDNA). Therefore, it is of interest to know whether this enzyme is critical for regulated gene activation. We report that the signal-dependent activation of gene transcription by nuclear receptors and other classes of DNA binding transcription factors, including activating protein 1, requires DNA topoisomerase IIbeta-dependent, transient, site-specific dsDNA break formation. Subsequent to the break, poly(adenosine diphosphate-ribose) polymerase-1 enzymatic activity is induced, which is required for a nucleosome-specific histone H1-high-mobility group B exchange event and for local changes of chromatin architecture. Our data mechanistically link DNA topoisomerase IIbeta-dependent dsDNA breaks and the components of the DNA damage and repair machinery in regulated gene transcription.
转录起始需要多种酶活性。DNA拓扑异构酶II与基因启动子区域相关联，并且能够在双链DNA（dsDNA）中产生断裂。因此，了解这种酶对于基因激活的调控是否至关重要是很有意义的。我们报告称，核受体以及其他类型的DNA结合转录因子（包括激活蛋白1）对基因转录的信号依赖性激活需要DNA拓扑异构酶IIβ依赖性的、瞬时的、位点特异性的dsDNA断裂形成。断裂之后，聚（腺苷二磷酸核糖）聚合酶-1的酶活性被诱导，这是核小体特异性组蛋白H1-高迁移率族B交换事件以及染色质结构局部变化所必需的。我们的数据在机制上将DNA拓扑异构酶IIβ依赖性dsDNA断裂与DNA损伤和修复机制的成分在基因转录调控中联系起来。
