Complex Relationships between Chromatin Accessibility, Sequence Divergence, and Gene Expression in Arabidopsis thaliana
Complex Relationships between Chromatin Accessibility, Sequence Divergence, and Gene Expression in Arabidopsis thaliana
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DOI：
10.1093/molbev/msx326
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发表时间：
2018-04-01
影响因子：
10.7
通讯作者：
Queitsch, Christin
中科院分区：
文献类型：
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作者：
Alexandre, Cristina M.;Urton, James R.;Queitsch, Christin
调节DNA的变异被认为是驱动表型变异、进化和疾病的原因。先前对动物物种中调控DNA和转录因子的研究突出了一个基本难题：转录因子结合结构域和同源结合位点是保守的，而调控DNA序列则不是。目前还不清楚保守的转录因子和动态调控位点如何产生跨物种的保守表达模式。在这里，我们探讨调节DNA的变化和其功能的后果，在拟南芥，使用染色质的可及性来描绘调节DNA全基因组。与以前的跨物种比较不同，调节DNA的位置同源性在A. thaliana生态型和较少的核苷酸分歧发生。在A. thaliana，我们发现15%的生态类型之间的可达性不同。其中一些可及性差异与广泛的，以前未注释的序列变异有关，包括许多缺失和古老的高变等位基因。出乎意料的是，对于大多数这样的调控位点，附近的基因表达不受影响。然而，具有高水平序列变异和差异染色质可及性的调控位点最有可能与差异基因表达相关。最后，也是最令人惊讶的是，我们发现绝大多数差异可及位点没有显示出潜在的序列变异。我们认为，这些令人惊讶的结果强调了在评估监管变异和预测其表型后果时考虑高阶监管背景的必要性。
Variation in regulatory DNA is thought to drive phenotypic variation, evolution, and disease. Prior studies of regulatory DNA and transcription factors across animal species highlighted a fundamental conundrum: Transcription factor binding domains and cognate binding sites are conserved, while regulatory DNA sequences are not. It remains unclear how conserved transcription factors and dynamic regulatory sites produce conserved expression patterns across species. Here, we explore regulatory DNA variation and its functional consequences within Arabidopsis thaliana, using chromatin accessibility to delineate regulatory DNA genome-wide. Unlike in previous cross-species comparisons, the positional homology of regulatory DNA is maintained among A. thaliana ecotypes and less nucleotide divergence has occurred. Of the similar to 50,000 regulatory sites in A. thaliana, we found that 15% varied in accessibility among ecotypes. Some of these accessibility differences were associated with extensive, previously unannotated sequence variation, encompassing many deletions and ancient hypervariable alleles. Unexpectedly, for the majority of such regulatory sites, nearby gene expression was unaffected. Nevertheless, regulatory sites with high levels of sequence variation and differential chromatin accessibility were the most likely to be associated with differential gene expression. Finally, and most surprising, we found that the vast majority of differentially accessible sites show no underlying sequence variation. We argue that these surprising results highlight the necessity to consider higher-order regulatory context in evaluating regulatory variation and predicting its phenotypic consequences.