来自美国斯坦福大学医学院遗传学系、斯坦福基因组技术研究中心(Stanford Genome Technology Center)、加拿大多伦多大学Terrence Donnelly细胞与生物分子研究中心的研究人员设计出了一种新的方法对酵母中70000个核小体(Nucleosomes)成功进行了描绘,获得了一张全新的酵母基因组图谱,这有助于我们了解和预测细胞的核小体状态,以及研究细胞遗传物质活动过程中的详细细节。这一研究成果公布在《自然—遗传学》(Nature Genetics)杂志上。
领导这一研究的是多伦多大学分子遗传学系、医学研究系的副教授Corey Nislow。在这篇文章中,Nislow领导的研究小组获得了一张完整的、三维的酵母基因组图谱。研究人员将这些信息输入电脑,建立了一个软件程序,帮助预测核小体会出现在细胞关键步骤中的哪儿——核小体在DNA翻译成蛋白之前会缠绕在DNA上,是一个细胞状态关键的指示核调控元件。在获得这一预测程序后,研究人员进一步证明了这一程序在预测核小体状态,以及细胞状态方面的重要作用。
Nislow表示,“当失去调控的时候,细胞就会产生错误的蛋白,或者进行不正确的分裂,这些在癌症之类的疾病细胞中都会出现”,“了解核小体出现在哪儿,是分辨细胞正在进行什么程序,将要进行什么活动的第一步,因此这个最初研究对于某些疾病的早期诊断意义重大。”
总而言之,科学家们可以通过了解核小体的状态判断哪些基因被激活,翻译成蛋白,而且这些信息可以作为疾病诊断的重要的第一步。
原始出处:
Nature Genetics 39, 1235 - 1244 (2007)
Published online: 16 September 2007 | doi:10.1038/ng2117
A high-resolution atlas of nucleosome occupancy in yeast
William Lee1,2, Desiree Tillo3, Nicolas Bray3, Randall H Morse4, Ronald W Davis1,2, Timothy R Hughes3,5,6 & Corey Nislow3,5,6
Abstract
We present the first complete high-resolution map of nucleosome occupancy across the whole Saccharomyces cerevisiae genome, identifying over 70,000 positioned nucleosomes occupying 81% of the genome. On a genome-wide scale, the persistent nucleosome-depleted region identified previously in a subset of genes demarcates the transcription start site. Both nucleosome occupancy signatures and overall occupancy correlate with transcript abundance and transcription rate. In addition, functionally related genes can be clustered on the basis of the nucleosome occupancy patterns observed at their promoters. A quantitative model of nucleosome occupancy indicates that DNA structural features may account for much of the global nucleosome occupancy.
Department of Genetics, Stanford University School of Medicine, Stanford, California 94305-5120, USA.
Stanford Genome Technology Center, 855 California Avenue, Palo Alto, California 94304, USA.
Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Wadsworth Center, New York State Department of Health, Albany, New York 12201-2002, USA.
Terrence Donnelly Centre for Cellular & Biomolecular Research, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
Banting and Best Department of Medical Research, 112 College St., Toronto, Ontario M5S 1L6, Canada.
Correspondence to: Corey Nislow3,5,6 e-mail: corey.nislow@utoronto.ca