The role of nucleosome positioning in the evolution of gene regulation.

The role of nucleosome positioning in the evolution of gene regulation.
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DOI:
10.1371/journal.pbio.1000414
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发表时间:
2010-07-06
期刊:
影响因子:
9.8
通讯作者:
Rando OJ
Rando OJ
中科院分区:
生物学1区
文献类型:
--
作者:
Tsankov AM;Thompson DA;Socha A;Regev A;Rando OJ

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一项比较基因组学研究绘制了12种真菌物种全基因组的核小体图谱,确定了将染色质结构变化与基因调控进化联系起来的多种不同机制。染色质组织在基因调控中起着重要作用,可以影响新的转录程序的功能和进化。然而,很难破译染色质组织变化的基础及其对基因表达的功能影响。在这里,我们通过测量12种半真菌酵母的mRNA丰度和核小体位置,对染色质组织和基因表达之间的关系进行了大规模的比较基因组分析。我们发现,在所有物种中,整体和功能性染色质组织都存在大量的保护,包括基因启动子处突出的核小体无区(NFRs),以及生长和应激基因中独特的染色质结构。染色质组织在全球定量特征(如相邻核小体之间的间距)和基因功能群方面也存在实质性分歧。表达水平、内在的抗核体序列和反式作用的染色质修饰因子在确定NFRs中都起着重要的、互补的和进化的作用。我们确定了染色质组织与基因调控进化相结合的五种机制,并促进了呼吸发酵和其他关键系统的进化,包括(1)与保守染色质组织相关的替代修饰剂的代偿进化,(2)从组成型NFRs逐渐过渡到反式调控的NFRs,(3)染色质组织和基因表达变化所伴随的内在抗核小体序列的丧失。(4)基序从NFRs重新定位到核小体封闭区域;(5)类似的激活因子-抑制因子对扩大了NFRs的使用。我们的研究揭示了染色质组织的分子基础,以及染色质组织在基因调控进化中的作用。基因调控的分化在生物进化中起着重要作用。有证据表明,真核生物基因组包装成染色质的变化可能是不同基因表达模式进化的基础。在这里,我们通过对12种酵母物种的核小体位置和mRNA水平的全基因组测量,探索了染色质结构在调节进化中的作用,这些物种跨越了2.5亿年的进化。我们发现了染色质结构变化与基因表达变化相关的几种不同方式。这些变化包括启动子可及性的变化,启动子染色质结构的变化,以及特定转录因子结合位点可及性的变化。在许多情况下,染色质结构的变化与生理多样性有关,包括以呼吸或发酵为基础的生活方式的进化、交配行为、耐盐性和基因组结构的广泛方面。总之,我们的数据将为未来研究染色质结构、基因调控和进化之间的相互作用提供丰富的资源。
A comparative genomics study maps nucleosomes across the entire genomes of 12 fungal species, identifying multiple distinct mechanisms linking changes in chromatin architecture to evolution of gene regulation. Chromatin organization plays a major role in gene regulation and can affect the function and evolution of new transcriptional programs. However, it can be difficult to decipher the basis of changes in chromatin organization and their functional effect on gene expression. Here, we present a large-scale comparative genomic analysis of the relationship between chromatin organization and gene expression, by measuring mRNA abundance and nucleosome positions genome-wide in 12 Hemiascomycota yeast species. We found substantial conservation of global and functional chromatin organization in all species, including prominent nucleosome-free regions (NFRs) at gene promoters, and distinct chromatin architecture in growth and stress genes. Chromatin organization has also substantially diverged in both global quantitative features, such as spacing between adjacent nucleosomes, and in functional groups of genes. Expression levels, intrinsic anti-nucleosomal sequences, and trans-acting chromatin modifiers all play important, complementary, and evolvable roles in determining NFRs. We identify five mechanisms that couple chromatin organization to evolution of gene regulation and have contributed to the evolution of respiro-fermentation and other key systems, including (1) compensatory evolution of alternative modifiers associated with conserved chromatin organization, (2) a gradual transition from constitutive to trans-regulated NFRs, (3) a loss of intrinsic anti-nucleosomal sequences accompanying changes in chromatin organization and gene expression, (4) re-positioning of motifs from NFRs to nucleosome-occluded regions, and (5) the expanded use of NFRs by paralogous activator-repressor pairs. Our study sheds light on the molecular basis of chromatin organization, and on the role of chromatin organization in the evolution of gene regulation. Divergence in gene regulation plays a major role in organismal evolution. Evidence suggests that changes in the packaging of eukaryotic genomes into chromatin can underlie the evolution of divergent gene expression patterns. Here, we explore the role of chromatin structure in regulatory evolution by whole-genome measurements of nucleosome positions and mRNA levels in 12 yeast species spanning ∼250 million years of evolution. We find several distinct ways in which changes in chromatin structure are associated with changes in gene expression. These include changes in promoter accessibility, changes in promoter chromatin architecture, and changes in the accessibility of specific transcription factor binding sites. In many cases, changes in chromatin architecture are coupled to physiological diversity, including the evolution of a respiration- or fermentation-based lifestyle, mating behavior, salt tolerance, and broad aspects of genomic structure. Together, our data will provide a rich resource for future investigations into the interplay between chromatin structure, gene regulation, and evolution.
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发表时间: 2008-12-26
期刊: MOLECULAR CELL
影响因子: 16
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发表时间: 2004-01-01
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