Department of Physics, Stanford University, Stanford, California.
Biophysics Program, Stanford University, Stanford, California.
Biophys J. 2020 Mar 24;118(6):1479-1488. doi: 10.1016/j.bpj.2020.01.034. Epub 2020 Feb 4.
A layer of dense heterochromatin is found at the periphery of the nucleus. Because this peripheral heterochromatin functions as a repressive phase, mechanisms that relocate genes to the periphery play an important role in regulating transcription. Using Monte Carlo simulations, we show that an interaction that attracts euchromatin and heterochromatin equally to the nuclear envelope will still preferentially locate heterochromatin to the nuclear periphery. This observation considerably broadens the class of possible interactions that result in peripheral positioning to include boundary interactions that either weakly attract all chromatin or strongly bind to a randomly chosen 0.05% of nucleosomes. The key distinguishing feature of heterochromatin is its high chromatin density with respect to euchromatin. In our model, this densification is caused by heterochromatin protein 1's preferential binding to histone H3 tails with a methylated lysine at the ninth residue, a hallmark of heterochromatin. We find that a global rearrangement of chromatin to place heterochromatin at the nuclear periphery can be accomplished by attaching a small subset of loci, even if these loci are uncorrelated with heterochromatin. Hence, factors that densify chromatin determine which genomic regions condense to form peripheral heterochromatin.
细胞核的外周存在一层致密的异染色质。由于这种外周异染色质起着抑制作用，因此将基因重新定位到外周的机制在转录调控中起着重要作用。通过蒙特卡罗模拟，我们发现一种可以平等地将常染色质和异染色质吸引到核膜的相互作用，仍然会优先将异染色质定位到核的外周。这一观察结果大大拓宽了可能导致外周定位的相互作用的类别，包括边界相互作用，这些相互作用要么微弱地吸引所有染色质，要么强烈地结合到随机选择的 0.05%的核小体。异染色质的关键区别特征是其相对于常染色质的高染色质密度。在我们的模型中，这种浓缩是由异染色质蛋白 1 优先与第九位赖氨酸甲基化的组蛋白 H3 尾巴结合引起的，这是异染色质的一个标志。我们发现，通过附着一小部分基因座，可以实现将异染色质重新排列到细胞核外周的全局重排，即使这些基因座与异染色质不相关。因此，使染色质浓缩的因素决定了哪些基因组区域会凝聚形成外周异染色质。
