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腾讯登录Nature & Nat Genet & Nat Biotechnol：三项研究揭示控制基因转录机制
| 导读 | 如今，来自美国西北大学物理科学肿瘤学中心(Physical Sciences-Oncology Center, PS-OC)的研究人员的三项开创性研究报道了他们在方法上取得的重要进步，这将使得人们更好地理解在正常细胞和癌细胞中，基因表达是如何受到调控的，同时也可能导致人们开发出更加有效的治疗试剂来治疗癌症病人。这三篇论文最近分别在<em>Nature Genetics</em&g... |
如今，来自美国西北大学物理科学肿瘤学中心(Physical Sciences-Oncology Center, PS-OC)的研究人员的三项开创性研究报道了他们在方法上取得的重要进步，这将使得人们更好地理解在正常细胞和癌细胞中，基因表达是如何受到调控的，同时也可能导致人们开发出更加有效的治疗试剂来治疗癌症病人。这三篇论文最近分别在<em>Nature Genetics</em>、<em>Nature Biotechnology</em>和<em>Nature</em>期刊上，可能有助于揭示控制基因转录的机制。
根据2006年发表在<em>Nature</em>期刊上一篇论文，通信作者 Jonathan Widom和Eran Segal 描述了一种绘制核小体的新方法。越来越清楚的是，在人体内，负责DNA组装成染色质的细胞装置发生突变是肿瘤产生的主要推动力。染色质是由DNA和蛋白组成的复合物，当遭受压缩时会形成染色体。这项研究允许人们阐述在细胞中染色质组装机制，从而有助于理解在癌症中是什么发生偏差和如何修复这种偏差。
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DNA第一密码就是DNA遗传密码，能够确定细胞蛋白的组成。2006年前，Widom和Segal就已在这篇论文中报道，他们发现第二种DNA密码能够解释DNA环绕着组蛋白复合物形成的线轴样结构--核小体--的布局。
根据2012年5月27日在线发表在<em>Nature Genetics</em>期刊上的一篇论文和2012年5月20日在线发表在<em>Nature Biotechnology</em>期刊上的另一篇论文，Segal研究小组开发出出一种优雅的实验系统：它能够允许他们准确地测量不利于核小体形成的DNA序列对转录调节的影响。这项新研究使得他们能够以一种规划好的和系统性的方式，同时导入上万个DNA序列区域到上万个活细胞之中---每个细胞导入一个DNA区域---，而且能够在一次实验中非常精准地和测量每个这样的变化产生的结果。利用这种系统，Segal研究小组证实促进核小体形成的DNA序列确实对转录产生显著性负面的影响。<<<相关论文参见：“<a href="http://www.nature.com/ng/journal/v44/n7/full/ng.2305.html" target="_blank">Manipulating nucleosome disfavoring sequences allows fine-tune regulation of gene expression in yeast</a>” 和“<a href="http://www.nature.com/nbt/journal/v30/n6/full/nbt.2205.html" target="_blank">Inferring gene regulatory logic from high-throughput measurements of thousands of systematically designed promoters</a>”。
根据第三篇于2012年6月3日在线发表在<em>Nature</em>期刊上的论文，研究人员描述了另一种方法上的主要进步。这种新技术允许他们比以前更加高精准地绘制核小体在基因组上的位置。这种技术不仅可以让人们更好地理解转录调控，同时它也应当有助于科学家们理解DNA生物学的基因特征。<<<相关论文参见：“<a href="http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11142.html" target="_blank">A map of nucleosome positions in yeast at base-pair resolution</a>”
本文编译自<a href="http://phys.org/news/2012-08-code-uncover-gene-transcription.html" target="_blank">More code cracking: Three studies help uncover the rules governing gene transcription</a>
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<a title="" href="http://dx.doi.org/10.1038/nbt.2205" target="_blank">doi: 10.1038/nbt.2205</a>
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<br/><strong>Inferring gene regulatory logic from high-throughput measurements of thousands of systematically designed promoters</strong><br/>
Eilon Sharon, Yael Kalma, Ayala Sharp, Tali Raveh-Sadka, Michal Levo, Danny Zeevi, Leeat Keren, Zohar Yakhini, Adina Weinberger & Eran Segal
Despite extensive research, our understanding of the rules according to which cis-regulatory sequences are converted into gene expression is limited. We devised a method for obtaining parallel, highly accurate gene expression measurements from thousands of designed promoters and applied it to measure the effect of systematic changes in the location, number, orientation, affinity and organization of transcription-factor binding sites and nucleosome-disfavoring sequences. Our analyses reveal a clear relationship between expression and binding-site multiplicity, as well as dependencies of expression on the distance between transcription-factor binding sites and gene starts which are transcription-factor specific, including a striking ~10-bp periodic relationship between gene expression and binding-site location. We show how this approach can measure transcription-factor sequence specificities and the sensitivity of transcription-factor sites to the surrounding sequence context, and compare the activity of 75 yeast transcription factors. Our method can be used to study both cis and trans effects of genotype on transcriptional, post-transcriptional and translational control.
<br/>来源：生物谷
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根据2006年发表在<em>Nature</em>期刊上一篇论文，通信作者 Jonathan Widom和Eran Segal 描述了一种绘制核小体的新方法。越来越清楚的是，在人体内，负责DNA组装成染色质的细胞装置发生突变是肿瘤产生的主要推动力。染色质是由DNA和蛋白组成的复合物，当遭受压缩时会形成染色体。这项研究允许人们阐述在细胞中染色质组装机制，从而有助于理解在癌症中是什么发生偏差和如何修复这种偏差。
<!--more-->
DNA第一密码就是DNA遗传密码，能够确定细胞蛋白的组成。2006年前，Widom和Segal就已在这篇论文中报道，他们发现第二种DNA密码能够解释DNA环绕着组蛋白复合物形成的线轴样结构--核小体--的布局。
根据2012年5月27日在线发表在<em>Nature Genetics</em>期刊上的一篇论文和2012年5月20日在线发表在<em>Nature Biotechnology</em>期刊上的另一篇论文，Segal研究小组开发出出一种优雅的实验系统：它能够允许他们准确地测量不利于核小体形成的DNA序列对转录调节的影响。这项新研究使得他们能够以一种规划好的和系统性的方式，同时导入上万个DNA序列区域到上万个活细胞之中---每个细胞导入一个DNA区域---，而且能够在一次实验中非常精准地和测量每个这样的变化产生的结果。利用这种系统，Segal研究小组证实促进核小体形成的DNA序列确实对转录产生显著性负面的影响。<<<相关论文参见：“<a href="http://www.nature.com/ng/journal/v44/n7/full/ng.2305.html" target="_blank">Manipulating nucleosome disfavoring sequences allows fine-tune regulation of gene expression in yeast</a>” 和“<a href="http://www.nature.com/nbt/journal/v30/n6/full/nbt.2205.html" target="_blank">Inferring gene regulatory logic from high-throughput measurements of thousands of systematically designed promoters</a>”。
根据第三篇于2012年6月3日在线发表在<em>Nature</em>期刊上的论文，研究人员描述了另一种方法上的主要进步。这种新技术允许他们比以前更加高精准地绘制核小体在基因组上的位置。这种技术不仅可以让人们更好地理解转录调控，同时它也应当有助于科学家们理解DNA生物学的基因特征。<<<相关论文参见：“<a href="http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11142.html" target="_blank">A map of nucleosome positions in yeast at base-pair resolution</a>”
本文编译自<a href="http://phys.org/news/2012-08-code-uncover-gene-transcription.html" target="_blank">More code cracking: Three studies help uncover the rules governing gene transcription</a>
<div id="ztload">
<div> </div>
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201208/2012080301044713.gif" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/10.1038/nbt.2205" target="_blank">doi: 10.1038/nbt.2205</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Inferring gene regulatory logic from high-throughput measurements of thousands of systematically designed promoters</strong><br/>
Eilon Sharon, Yael Kalma, Ayala Sharp, Tali Raveh-Sadka, Michal Levo, Danny Zeevi, Leeat Keren, Zohar Yakhini, Adina Weinberger & Eran Segal
Despite extensive research, our understanding of the rules according to which cis-regulatory sequences are converted into gene expression is limited. We devised a method for obtaining parallel, highly accurate gene expression measurements from thousands of designed promoters and applied it to measure the effect of systematic changes in the location, number, orientation, affinity and organization of transcription-factor binding sites and nucleosome-disfavoring sequences. Our analyses reveal a clear relationship between expression and binding-site multiplicity, as well as dependencies of expression on the distance between transcription-factor binding sites and gene starts which are transcription-factor specific, including a striking ~10-bp periodic relationship between gene expression and binding-site location. We show how this approach can measure transcription-factor sequence specificities and the sensitivity of transcription-factor sites to the surrounding sequence context, and compare the activity of 75 yeast transcription factors. Our method can be used to study both cis and trans effects of genotype on transcriptional, post-transcriptional and translational control.
<br/>来源：生物谷
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