Regulation of the boundaries of accessible chromatin.
Regulation of the boundaries of accessible chromatin.
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DOI：
10.1371/journal.pgen.1003778
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Choi JK
中科院分区：
文献类型：
--
作者：
Chai X;Nagarajan S;Kim K;Lee K;Choi JK
调控区维持核小体耗尽、开放的染色质状态，但同时需要核小体的存在以进行特定的组蛋白修饰。目前尚不清楚如何实现这些目标，以发挥适当的监管职能。在这里，我们表明，核小体定位在接近染色质区域的边界附近提供了组蛋白修饰的平台，同时防止闭塞的调控元件。这些边界核小体特别富含人类中的活性或潜在调节标记，例如组蛋白乙酰化、H3K4甲基化、H3K9me3、H3K79me2和H4K20me1。此外，我们发现，基于全基因组分析的1000重组酵母菌株，开放的染色质边界的位置往往变化大部分在150 bp的遗传扰动后，而这种位置的变化增加成比例的序列偏好的基础DNA的核小体形成。超过40%的本地边界的变化与顺式或反式作用因子的遗传变异。一个相当大的比例，已确定的遗传因素也与附近的基因表达，这是相关的转录起始位点（tss）和边界之间的距离，面对的tss。两者合计，在可接近的染色质区域的宽度的变化可能会出现在与边界核小体的翻译后修饰或染色质调节剂的调制，并与附近的基因转录的活性相关联。开放染色质的形成和调控与核小体的重塑和修饰密切相关。调控区如启动子和增强子维持无核小体的开放染色质状态，同时核小体的存在是特定组蛋白修饰所必需的。在这项工作中，我们进行了详细的分析，我们的开放染色质图谱的数据为100个不同的酵母菌株和全基因组核小体占有沿着的开放染色质和核小体定位在人类中产生的公开数据在ENCODE项目。我们观察到核小体位于靠近其边界的可接近的染色质区域内。这些边界核小体似乎携带各种组蛋白甲基化，而不妨碍DNA调节剂的结合，这些核小体的序列偏好与可接近的染色质宽度的变化有关。开放的染色质结构域的末端位置，特别是与核小体形成的高内在偏好，是更灵活的比中间点，改变大多在150 bp的遗传扰动。通过使用数量性状基因座（QTL）定位，我们确定了与开放染色质宽度变化相关的遗传变异，并研究了其与附近基因表达的关系。
Regulatory regions maintain nucleosome-depleted, open chromatin status but simultaneously require the presence of nucleosomes for specific histone modifications. It remains unclear how these can be achieved for proper regulatory function. Here we demonstrate that nucleosomes positioned within accessible chromatin regions near the boundaries provide platforms for histone modifications while preventing the occlusion of regulatory elements. These boundary nucleosomes were particularly enriched for active or poised regulatory marks in human, such as histone acetylations, H3K4 methylations, H3K9me3, H3K79me2, and H4K20me1. Additionally, we found that based on a genome-wide profiling of ∼100 recombinant yeast strains, the location of open chromatin borders tends to vary mostly within 150 bp upon genetic perturbation whereas this positional variation increases in proportion to the sequence preferences of the underlying DNA for nucleosome formation. More than 40% of the local boundary shifts were associated with genetic variation in cis- or trans-acting factors. A sizeable fraction of the identified genetic factors was also associated with nearby gene expression, which was correlated with the distance between the transcription start site (tss) and the boundary that faces the tss. Taken together, the variation in the width of accessible chromatin regions may arise in conjunction with the modulation of the boundary nucleosomes by post-translational modifications or by chromatin regulators and in association with the activity of nearby gene transcription. Open chromatin formation and regulation are intimately coupled with nucleosome remodelling and modification. Regulatory regions such as promoters and enhancers maintain nucleosome-free, open chromatin states whilst at the same time the presence of nucleosomes is required for specific histone modifications. In this work, we carried out detailed analyses of our data of open chromatin maps for ∼100 different yeast strains and whole-genome nucleosome occupancy along with the public data of open chromatin and nucleosome positioning in human generated in the ENCODE project. We observed nucleosomes positioned within accessible chromatin regions near their boundaries. These boundary nucleosomes appeared to carry various histone methylations without hampering the binding of DNA regulators and sequence preferences for these nucleosomes were associated with variation in the width of accessible chromatin. The end positions of open chromatin domains, particularly with high intrinsic preferences for nucleosome formation, were more flexible than the middle point, changing mostly within 150 bp upon genetic perturbation. By using quantitative trait loci (QTL) mapping, we identified genetic variants that are associated with the variation in the width of open chromatin and examined its relationship with nearby gene expression.
影响因子：
4.4
作者：
Dai Z;Dai X;Xiang Q;Feng J;Wang J;Deng Y;He C
通讯作者：
He C