Gervais Alain L, Gaudreau Luc
Département de Biologie, Université de Sherbrooke, Sherbrooke, Québec, Canada.
BMC Mol Biol. 2009 Mar 4;10:18. doi: 10.1186/1471-2199-10-18.
Nucleosomes are nucleoproteic complexes, formed of eight histone molecules and DNA, and they are responsible for the compaction of the eukaryotic genome. Their presence on DNA influences many cellular processes, such as transcription, DNA replication, and DNA repair. The evolutionarily conserved histone variant H2A.Z alters nucleosome stability and is highly enriched at gene promoters. Its localization to specific genomic loci in human cells is presumed to depend either on the underlying DNA sequence or on a certain epigenetic modification pattern.
We analyzed the differences in histone post-translational modifications and DNA sequences near nucleosomes that do or do not contain H2A.Z. We show that both the epigenetic context and underlying sequences can be used to classify nucleosomal regions, with highly significant accuracy, as likely to either contain H2A.Z or canonical histone H2A. Furthermore, our models accurately recapitulate the observed nucleosome occupancy near the transcriptional start sites of human promoters.
We conclude that both genetic and epigenetic features are likely to participate in targeting H2A.Z to distinct chromatin loci.
核小体是由八个组蛋白分子和DNA组成的核蛋白复合物,它们负责真核生物基因组的压缩。它们在DNA上的存在会影响许多细胞过程,如转录、DNA复制和DNA修复。进化上保守的组蛋白变体H2A.Z会改变核小体稳定性,并且在基因启动子处高度富集。据推测,其在人类细胞中特定基因组位点的定位要么取决于潜在的DNA序列,要么取决于某种表观遗传修饰模式。
我们分析了含有或不含有H2A.Z的核小体附近组蛋白翻译后修饰和DNA序列的差异。我们表明,表观遗传背景和潜在序列都可用于以高度显著的准确性将核小体区域分类为可能含有H2A.Z或典型组蛋白H2A。此外,我们的模型准确地重现了在人类启动子转录起始位点附近观察到的核小体占有率。
我们得出结论,遗传和表观遗传特征都可能参与将H2A.Z靶向不同的染色质位点。