Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720
Proc Natl Acad Sci U S A. 2020 Nov 3;117(44):27493-27501. doi: 10.1073/pnas.2004111117. Epub 2020 Oct 19.
Heterochromatic domains are complex structures composed of nucleosome arrays that are bound by silencing factors. This composition raises the possibility that certain configurations of nucleosome arrays facilitate heterochromatic silencing. We tested this possibility in by systematically altering the distance between heterochromatic nucleosome-depleted regions (NDRs), which is predicted to affect local nucleosome positioning by limiting how nucleosomes can be packed between NDRs. Consistent with this prediction, serial deletions that altered the distance between heterochromatic NDRs revealed a striking oscillatory relationship between inter-NDR distance and defects in nucleosome positioning. Furthermore, conditions that caused poor nucleosome positioning also led to defects in both heterochromatin stability and the ability of cells to generate and inherit epigenetic transcriptional states. These findings strongly suggest that nucleosome positioning can contribute to formation and maintenance of functional heterochromatin and point to previously unappreciated roles of NDR positioning within heterochromatic domains.
异染色质域是由核小体阵列组成的复杂结构，这些核小体阵列被沉默因子所结合。这种组成提出了这样一种可能性，即核小体阵列的某些特定构象有利于异染色质沉默。我们通过系统改变异染色质核小体耗尽区（NDR）之间的距离来检验这种可能性，这预计会通过限制核小体在 NDR 之间的组装方式来影响局部核小体定位。与这一预测一致，改变异染色质 NDR 之间距离的连续缺失揭示了 NDR 之间的距离与核小体定位缺陷之间存在惊人的振荡关系。此外，导致核小体定位不良的条件也导致异染色质稳定性缺陷以及细胞产生和遗传表观遗传转录状态的能力缺陷。这些发现强烈表明核小体定位有助于功能性异染色质的形成和维持，并指出了 NDR 在异染色质域内的以前未被认识到的作用。
