Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
Mol Cell. 2022 Jun 2;82(11):2098-2112.e4. doi: 10.1016/j.molcel.2022.04.026. Epub 2022 May 20.
The critical role of the INO80 chromatin remodeling complex in transcription is commonly attributed to its nucleosome sliding activity. Here, we have found that INO80 prefers to mobilize hexasomes over nucleosomes. INO80's preference for hexasomes reaches up to ∼60 fold when flanking DNA overhangs approach ∼18-bp linkers in yeast gene bodies. Correspondingly, deletion of INO80 significantly affects the positions of hexasome-sized particles within yeast genes in vivo. Our results raise the possibility that INO80 promotes nucleosome sliding by dislodging an H2A-H2B dimer, thereby making a nucleosome transiently resemble a hexasome. We propose that this mechanism allows INO80 to rapidly mobilize nucleosomes at promoters and hexasomes within gene bodies. Rapid repositioning of hexasomes that are generated in the wake of transcription may mitigate spurious transcription. More generally, such versatility may explain how INO80 regulates chromatin architecture during the diverse processes of transcription, replication, and repair.
INO80 染色质重塑复合物在转录中的关键作用通常归因于其核小体重塑活性。在这里，我们发现 INO80 更喜欢移动六聚体而不是核小体。当侧翼 DNA 突出接近酵母基因体中约 18 个碱基的连接子时，INO80 对六聚体的偏好达到了约 60 倍。相应地，INO80 的缺失显著影响了体内酵母基因中六聚体大小颗粒的位置。我们的结果提出了一种可能性，即 INO80 通过驱逐 H2A-H2B 二聚体来促进核小体滑动，从而使核小体暂时类似于六聚体。我们提出，这种机制允许 INO80 在启动子和基因体内部快速移动核小体。转录后生成的六聚体的快速重定位可能减轻了转录的错误。更一般地说，这种多功能性可以解释 INO80 如何在转录、复制和修复等各种过程中调节染色质结构。
