The organization of nucleosomes around splice sites.

The organization of nucleosomes around splice sites.
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DOI:
10.1093/nar/gkq007
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发表时间:
2010-05
影响因子:
14.9
通讯作者:
Zhang L
Zhang L
中科院分区:
生物学2区
文献类型:
--
作者:
Chen W;Luo L;Zhang L

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核小体沿着染色体的占据是基因调控的关键因素。然而,在哺乳动物基因组中,除了启动子区域外,核小体组织的全基因组性质和功能仍不清楚。利用从微阵列数据中训练的二次判别式多样性增量(IDQD)计算模型,定义了核小体占有分数(NOScore),并将其应用于人类基因组中组成型、盒式外显子、选择性3′和5′剪接事件的剪接点区域。我们发现NOScore和RNA剪接之间存在一个有趣的关系:在组成性和选择性剪接事件中,外显子区域的NOScore均高于其侧翼内含子序列,表明外显子区域具有更强的核小体占据潜力。此外,在所有剪接事件中,NOScore谷存在于受体位点上游约25 bp处。通过定义折叠多样性与能量比来描述RNA结构的灵活性,我们证明了来自核小体占据区域的初级RNA转录物是相对刚性的,而来自核小体耗尽区域的初级RNA转录物是相对柔性的。DNA序列的核小体占据/消耗与剪接点周围的初级转录物的结构柔性/刚性之间的负相关性可能为更深入地理解核小体组织在RNA剪接调控中的意想不到的作用提供线索。
The occupancy of nucleosomes along chromosome is a key factor for gene regulation. However, except promoter regions, genome-wide properties and functions of nucleosome organization remain unclear in mammalian genomes. Using the computational model of Increment of Diversity with Quadratic Discriminant (IDQD) trained from the microarray data, the nucleosome occupancy score (NOScore) was defined and applied to splice junction regions of constitutive, cassette exon, alternative 3′ and 5′ splicing events in the human genome. We found an interesting relation between NOScore and RNA splicing: exon regions have higher NOScores compared with their flanking intron sequences in both constitutive and alternative splicing events, indicating the stronger nucleosome occupation potential of exon regions. In addition, NOScore valleys present at ∼25 bp upstream of the acceptor site in all splicing events. By defining folding diversity-to-energy ratio to describe RNA structural flexibility, we demonstrated that primary RNA transcripts from nucleosome occupancy regions are relatively rigid and those from nucleosome depleted regions are relatively flexible. The negative correlation between nucleosome occupation/depletion of DNA sequence and structural flexibility/rigidity of its primary transcript around splice junctions may provide clues to the deeper understanding of the unexpected role for nucleosome organization in the regulation of RNA splicing.
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