Department of Biological Science, The Florida State University, Tallahassee, Florida 32306-4295, USA;
Genome Res. 2014 Feb;24(2):251-9. doi: 10.1101/gr.160150.113. Epub 2013 Dec 5.
Nucleosome occupancy plays a key role in regulating access to eukaryotic genomes. Although various chromatin regulatory complexes are known to regulate nucleosome occupancy, the role of DNA sequence in this regulation remains unclear, particularly in mammals. To address this problem, we measured nucleosome distribution at high temporal resolution in human cells at hundreds of genes during the reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV). We show that nucleosome redistribution peaks at 24 h post-KSHV reactivation and that the nucleosomal redistributions are widespread and transient. To clarify the role of DNA sequence in these nucleosomal redistributions, we compared the genes with altered nucleosome distribution to a sequence-based computer model and in vitro-assembled nucleosomes. We demonstrate that both the predicted model and the assembled nucleosome distributions are concordant with the majority of nucleosome redistributions at 24 h post-KSHV reactivation. We suggest a model in which loci are held in an unfavorable chromatin architecture and "spring" to a transient intermediate state directed by DNA sequence information. We propose that DNA sequence plays a more considerable role in the regulation of nucleosome positions than was previously appreciated. The surprising findings that nucleosome redistributions are widespread, transient, and DNA-directed shift the current perspective regarding regulation of nucleosome distribution in humans.
核小体占据在调节真核基因组的可及性方面起着关键作用。尽管已知各种染色质调节复合物可调节核小体占据，但 DNA 序列在这种调节中的作用仍不清楚，特别是在哺乳动物中。为了解决这个问题，我们在人类细胞中数百个基因的数百个基因在卡波西肉瘤相关疱疹病毒（KSHV）再激活过程中以高时间分辨率测量了核小体分布。我们表明核小体再分布在 KSHV 再激活后 24 小时达到峰值，并且核小体再分布广泛且短暂。为了阐明 DNA 序列在这些核小体再分布中的作用，我们将具有改变的核小体分布的基因与基于序列的计算机模型和体外组装的核小体进行了比较。我们证明，预测模型和组装核小体的分布与 KSHV 再激活后 24 小时大多数核小体再分布一致。我们提出了一种模型，其中位点处于不利的染色质结构中，并由 DNA 序列信息指导“弹回”到短暂的中间状态。我们提出 DNA 序列在调节核小体位置方面的作用比以前认为的更为重要。核小体再分布广泛、短暂且 DNA 导向的这一惊人发现改变了人们对人类核小体分布调节的看法。
