Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Nucleic Acids Res. 2023 May 8;51(8):3671-3678. doi: 10.1093/nar/gkad079.
The exceptionally high positive charge of the histones, concentrated in the N- and C-terminal tails, is believed to contribute to the stability of the nucleosome by neutralizing the negative charge of the nucleosomal DNA. We find, on the contrary, that the high positive charge contributes to instability, performing an essential function in chromatin remodeling. We show that the tails are required for removal of the histone octamer by the RSC chromatin remodeling complex, and this function is not due to direct RSC-tail interaction. We also show that the tails are required for histone octamer transfer from nucleosomes to DNA, and this activity of the tails is a consequence of their positive charge. Thus, the histone tails, intrinsically disordered protein regions, perform a critical role in chromatin structure and transcription, unrelated to their well-known role in regulation through posttranscriptional modification.
组蛋白异常高的正电荷集中在 N-末端和 C-末端尾部,被认为通过中和核小体 DNA 的负电荷来有助于核小体的稳定性。相反,我们发现高正电荷有助于不稳定性,并在染色质重塑中发挥重要功能。我们表明,尾部对于 RSC 染色质重塑复合物去除组蛋白八聚体是必需的,并且该功能不是由于 RSC-尾部直接相互作用。我们还表明,尾部对于组蛋白八聚体从核小体转移到 DNA 是必需的,并且尾部的这种活性是其正电荷的结果。因此,组蛋白尾部,本质上是无规卷曲的蛋白质区域,在染色质结构和转录中发挥关键作用,与它们通过转录后修饰调节的已知作用无关。