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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Transcriptional Regulation Constrains The Organization Of Genes On Eukaryotic Chromosomes
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Transcriptional Regulation Constrains The Organization Of Genes On Eukaryotic Chromosomes

机译：转录调控限制真核染色体上基因的组织。

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摘要

Genetic material in eukaryotes is tightly packaged in a hierarchical manner into multiple linear chromosomes within the nucleus. Although it is known that eukaryotic transcriptional regulation is complex and requires an intricate coordination of several molecular events both in space and time, whether the complexity of this process constrains genome organization is still unknown. Here, we present evidence for the existence of a higher-order organization of genes across and within chromosomes that is constrained by transcriptional regulation. In particular, we reveal that the target genes (TGs) of transcription factors (TFs) for the yeast, Saccharo-myces cerevisiae, are encoded in a highly ordered manner both across and within the 16 chromosomes. We show that (ⅰ) the TGs of a majority of TFs show a strong preference to be encoded on specific chromosomes, (ⅱ) the TGs of a significant number of TFs display a strong preference (or avoidance) to be encoded in regions containing particular chromosomal landmarks such as telomeres and centromeres, and (ⅲ) the TGs of most TFs are positionally clustered within a chromosome. Our results demonstrate that specific organization of genes that allowed for efficient control of transcription within the nuclear space has been selected during evolution. We anticipate that uncovering such higher-order organization of genes in other eukaryotes will provide insights into nuclear architecture, and will have implications in genetic engineering experiments, gene therapy, and understanding disease conditions that involve chromosomal aberrations.
机译：真核生物中的遗传物质以分层的方式紧密地包装在细胞核内的多个线性染色体中。尽管已知真核转录调控是复杂的并且需要时空上几个分子事件的复杂协调，但是这个过程的复杂性是否会限制基因组的组织仍然是未知的。在这里，我们提供证据表明存在遍及染色体内和受转录调控限制的基因的更高阶组织。特别是，我们揭示了酵母Saccharo-myces cerevisiae的转录因子（TFs）的目标基因（TGs）在16个染色体之间和内部以高度有序的方式编码。我们显示（ⅰ）大多数TF的TG显示出在特定染色体上编码的强烈偏好，（ⅱ）大量TF的TG显示出在包含特定染色体的区域中编码的强烈偏好（或避免）。染色体标志物（例如端粒和着丝粒）以及（TF）大多数TF的TG都在染色体内位置聚集。我们的结果表明，在进化过程中已选择了能够有效控制核空间内转录的基因的特定组织。我们预期发现在其他真核生物中发现这种基因的更高层次的组织将提供对核结构的见识，并将对基因工程实验，基因治疗以及了解涉及染色体畸变的疾病状况产生影响。

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