A hexasome is the preferred substrate for the INO80 chromatin remodeling complex, allowing versatility of function.
A hexasome is the preferred substrate for the INO80 chromatin remodeling complex, allowing versatility of function.
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DOI：
10.1016/j.molcel.2022.04.026
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发表时间：
2022-06-02
期刊：
影响因子：
16
通讯作者：
Narlikar, Geeta J.
中科院分区：
文献类型：
--
作者：
Hsieh, Laura J.;Gourdet, Muryam A.;Moore, Camille M.;Munoz, Elise N.;Gamarra, Nathan;Ramani, Vijay;Narlikar, Geeta J.
INO 80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滑动活性。在这里，我们发现INO 80更喜欢动员六酶体而不是核小体。当侧翼DNA突出端接近酵母基因体中的~18-bp接头时，INO 80对六酶体的偏好达到~60倍。相应地，INO 80的缺失显著影响了体内酵母基因内六酶体大小颗粒的位置。我们的研究结果提高了INO 80通过驱逐H2 A-H2 B二聚体促进核小体滑动的可能性，从而使核小体瞬时类似于六酶体。我们建议，这种机制允许INO 80迅速动员核小体在基因体内的启动子和六酶体。在转录后产生的六酶体的快速重新定位可以减轻假转录。更一般地说，这种多功能性可以解释INO 80如何在转录，复制和修复的不同过程中调节染色质结构。新出现的证据表明，在转录过程中在基因体中形成六酶体。这些粒子是如何被调节的，人们还知之甚少。在这里，Hsieh等人使用机械酶学和基因组学来表明，与核小体相比，INO 80重塑剂在体外优先滑动六酶体，并影响六酶体在体内的定位。
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. Emerging evidence shows that hexasomes are formed in gene bodies during transcription. How these particles are regulated is poorly understood. Here, Hsieh et al. use mechanistic enzymology and genomics to show that the INO80 remodeler preferentially slides hexasomes compared with nucleosomes in vitro and affects hexasome positioning in vivo.
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