Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Cell Chem Biol. 2019 Oct 17;26(10):1436-1449.e5. doi: 10.1016/j.chembiol.2019.08.002. Epub 2019 Aug 22.
RNA associates extensively with chromatin and can influence its structure; however, the potential role of the negative charges of RNA on chromatin structure remains unknown. Here, we demonstrate that RNA prevents precipitation of histones and can attenuate electrostatic interactions between histones and DNA, thereby loosening up the chromatin structure. This effect is independent of the sequence of RNA but dependent on its single-stranded nature, length, concentration, and negative charge. Opening and closure of chromatin by RNA occurs rapidly (within minutes) and passively (in permeabilized cells), in agreement with electrostatics. Accordingly, chromatin compaction following removal of RNA can be prevented by high ionic strength or neutralization of the positively charged histone tails by hyperacetylation. Finally, LINE1 repeat RNAs bind histone H2B and can decondense chromatin. We propose that RNA regulates chromatin opening and closure by neutralizing the positively charged tails of histones, reducing their electrostatic interactions with DNA.
RNA 与染色质广泛结合，并能影响其结构；然而，RNA 的负电荷对染色质结构的潜在作用仍不清楚。在这里，我们证明 RNA 可以防止组蛋白沉淀，并能减弱组蛋白与 DNA 之间的静电相互作用，从而使染色质结构变得松散。这种效应不依赖于 RNA 的序列，而是依赖于其单链性质、长度、浓度和负电荷。RNA 打开和关闭染色质的过程非常迅速（几分钟内）且被动（在通透化细胞中），这与静电作用一致。因此，通过高离子强度或通过过度乙酰化使带正电荷的组蛋白尾部中和，可以防止 RNA 去除后染色质的紧缩。最后，LINE1 重复 RNA 与组蛋白 H2B 结合，并能使染色质解凝聚。我们提出，RNA 通过中和组蛋白带正电荷的尾部来调节染色质的开闭，从而减少它们与 DNA 的静电相互作用。
