Dipartimento di Matematica ed Informatica, Università degli Studi di Palermo, Palermo, Italy.
Computational Biology Center, IBM T. J. Watson Research, Yorktown Heights, NY, USA.
Bioinformatics. 2018 Oct 15;34(20):3454-3460. doi: 10.1093/bioinformatics/bty799.
Although the nucleosome occupancy along a genome can be in part predicted by in vitro experiments, it has been recently observed that the chromatin organization presents important differences in vitro with respect to in vivo. Such differences mainly regard the hierarchical and regular structures of the nucleosome fiber, whose existence has long been assumed, and in part also observed in vitro, but that does not apparently occur in vivo. It is also well known that the DNA sequence has a role in determining the nucleosome occupancy. Therefore, an important issue is to understand if, and to what extent, the structural differences in the chromatin organization between in vitro and in vivo have a counterpart in terms of the underlying genomic sequences.
We present the first quantitative comparison between the in vitro and in vivo nucleosome maps of two model organisms (S. cerevisiae and C. elegans). The comparison is based on the construction of weighted k-mer dictionaries. Our findings show that there is a good level of sequence conservation between in vitro and in vivo in both the two organisms, in contrast to the abovementioned important differences in chromatin structural organization. Moreover, our results provide evidence that the two organisms predispose themselves differently, in terms of sequence composition and both in vitro and in vivo, for the nucleosome occupancy. This leads to the conclusion that, although the notion of a genome encoding for its own nucleosome occupancy is general, the intrinsic histone k-mer sequence preferences tend to be species-specific.
The files containing the dictionaries and the main results of the analysis are available at http://math.unipa.it/rombo/material.
Supplementary data are available at Bioinformatics online.
尽管核小体在基因组上的占有率可以部分通过体外实验预测，但最近观察到，与体内相比，染色质组织在体外呈现出重要的差异。这些差异主要涉及核小体纤维的层次和规则结构，这种结构的存在早已被假设，部分也在体外观察到，但在体内显然不存在。众所周知，DNA 序列在决定核小体占有率方面起着作用。因此，一个重要的问题是要了解在体内和体外染色质组织的结构差异在多大程度上与潜在的基因组序列相对应。
我们首次对两种模式生物（酿酒酵母和秀丽隐杆线虫）的体外和体内核小体图谱进行了定量比较。这种比较是基于构建加权 k-mer 字典。我们的发现表明，在两种生物中，体内和体外的序列都有很好的保守性，而染色质结构组织的上述重要差异则相反。此外，我们的结果提供了证据，表明这两种生物在序列组成方面以及在体内和体外都以不同的方式为核小体占有率做好了准备。这就得出了这样的结论，尽管基因组编码自身核小体占有率的概念是普遍的，但内在的组蛋白 k-mer 序列偏好往往是物种特异性的。
包含字典和分析主要结果的文件可在 http://math.unipa.it/rombo/material 上获得。
补充数据可在生物信息学在线获得。
