Jamai Adil, Puglisi Andrea, Strubin Michel
Department of Microbiology and Molecular Medicine, University Medical Centre, Geneva, Switzerland.
Mol Cell. 2009 Aug 14;35(3):377-83. doi: 10.1016/j.molcel.2009.07.001.
Nucleosomes are surprisingly dynamic structures in vivo, showing transcription-independent exchange of histones H2A-H2B genome-wide and exchange of H3-H4 mainly within the promoters of transcribed genes. In addition, nucleosomes are disrupted in front of and reassembled behind the elongating RNA polymerase. Here we show that inactivation of histone chaperone Spt16 in yeast results in rapid loss of H2B and H3 from transcribed genes but also from inactive genes. In all cases, histone loss is blocked by a transcription inhibitor, indicating a transcription-dependent event. Thus, nucleosomes are efficiently evicted by the polymerase but do not reform in the absence of Spt16. Yet exchange of nucleosomal H2B with free histones occurs normally, and, unexpectedly, incorporation of new H3 increases at all loci tested. This points to Spt16 restoring normal nucleosome structure by redepositing the displaced H3-H4 histones, thereby preventing incorporation of new histones and perhaps changes in histone modification patterns associated with ongoing transcription.
核小体在体内是非常动态的结构，在全基因组范围内呈现出与转录无关的组蛋白H2A - H2B交换，而H3 - H4的交换主要发生在转录基因的启动子区域内。此外，核小体在延伸的RNA聚合酶前方被破坏，并在其后方重新组装。我们在此表明，酵母中组蛋白伴侣Spt16的失活导致转录基因以及非活性基因中的H2B和H3迅速丢失。在所有情况下，组蛋白的丢失都被转录抑制剂所阻断，表明这是一个依赖转录的事件。因此，核小体被聚合酶有效地驱逐，但在没有Spt16的情况下不会重新形成。然而，核小体H2B与游离组蛋白的交换正常发生，并且出乎意料的是，在所有测试位点，新H3的掺入都增加了。这表明Spt16通过重新沉积被置换的H3 - H4组蛋白来恢复正常的核小体结构，从而防止新组蛋白的掺入，并可能防止与正在进行的转录相关的组蛋白修饰模式的变化。
