Prajapati Hemant K, Xu Zhuwei, Eriksson Peter R, Clark David J
Division of Developmental Biology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA.
Nat Commun. 2025 May 16;16(1):4577. doi: 10.1038/s41467-025-59994-7.
The eukaryotic genome is packaged into chromatin, which is composed of a nucleosomal filament that coils up to form more compact structures. Chromatin exists in two main forms: euchromatin, which is relatively decondensed and enriched in transcriptionally active genes, and heterochromatin, which is condensed and transcriptionally repressed. It is widely accepted that chromatin architecture modulates DNA accessibility, restricting the access of sequence-specific, gene-regulatory, transcription factors to the genome. However, the evidence for this model derives primarily from experiments with isolated nuclei, in which chromatin remodeling has ceased, resulting in a static chromatin structure. Here, using a DNA methyltransferase to measure accessibility in vivo, we show that both euchromatin and heterochromatin are fully accessible in living human cells, whereas centromeric α-satellite chromatin is partly inaccessible. We conclude that all nucleosomes in euchromatin and heterochromatin are highly dynamic in living cells, except for nucleosomes in centromeric chromatin.
真核生物基因组被包装成染色质，染色质由核小体细丝组成，核小体细丝盘绕形成更紧密的结构。染色质主要以两种形式存在：常染色质，其相对解聚且富含转录活性基因；异染色质，其凝聚且转录受抑制。人们普遍认为染色质结构调节DNA可及性，限制序列特异性、基因调控转录因子对基因组的接近。然而，该模型的证据主要来自对分离细胞核的实验，在这些实验中染色质重塑已经停止，导致染色质结构静态化。在这里，我们使用DNA甲基转移酶在体内测量可及性，结果表明常染色质和异染色质在活的人类细胞中都是完全可及的，而着丝粒α卫星染色质部分不可及。我们得出结论，除着丝粒染色质中的核小体外，常染色质和异染色质中的所有核小体在活细胞中都是高度动态的。
