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Chromatin compaction leads to a preference for peripheral heterochromatin
Biophysical Journal ( IF 3.2 ) Pub Date : 2020-03-01 , DOI: 10.1016/j.bpj.2020.01.034
Quinn MacPherson 1 , Bruno Beltran 2 , Andrew J Spakowitz 3
Affiliation  

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.

中文翻译:

染色质压缩导致偏爱外周异染色质

在细胞核的外围发现了一层致密的异染色质。由于这种外周异染色质起到抑制相的作用,因此将基因重新定位到外周的机制在调节转录中起重要作用。使用蒙特卡罗模拟,我们表明,将常染色质和异染色质同等地吸引到核膜的相互作用仍将优先将异染色质定位到核外围。这一观察结果大大拓宽了导致外围定位的可能相互作用的类别,包括边界相互作用,这些相互作用要么弱吸引所有染色质,要么强烈结合随机选择的 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,这种致密化是由异染色质蛋白 1 优先结合组蛋白 H3 尾部和第九个残基处的甲基化赖氨酸引起的,这是异染色质的标志。我们发现,即使这些基因座与异染色质不相关,也可以通过附加一小部分基因座来实现染色质的全局重排,以将异染色质置于核外围。因此,致密染色质的因素决定了哪些基因组区域浓缩形成外周异染色质。即使这些基因座与异染色质不相关。因此,致密染色质的因素决定了哪些基因组区域浓缩形成外周异染色质。即使这些基因座与异染色质不相关。因此,致密染色质的因素决定了哪些基因组区域浓缩形成外周异染色质。
更新日期:2020-03-01
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