在人体内对人类保存的非编码序列进行体内增强剂分析
Len A Pennacchio1, Nadav Ahituv, Alan M Moses
1US Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA. LAPennacchio@lbl.gov
Nature
|November 7, 2006
概括
研究人员使用进化保护确定了基因调节元件. 许多保存的序列起到增强作用,特别是在发育中的神经系统中,有助于基因组注释.
科学领域:
- 基因组学就是基因组学.
- 发展生物学 发展生物学
- 进化生物学 进化生物学
背景情况:
- 识别基因调节元件对于脊椎动物基因组注释至关重要.
- 缺乏经过实验验证的培训套件,阻碍了在体内定义基因调控功能的进展.
研究的目的:
- 识别和描述人体基因组中保存的非编码元素的体内增强剂活性.
- 扩大特征人类基因增强剂的目录,并创建验证的训练套件.
主要方法:
- 利用极端的进化序列保护 (人-气泡鱼,人-老鼠-老鼠) 来过假定的基因调控元素.
- 在胚胎日11.5.5使用转基因小鼠增强剂试验测试了167个高度保守的非编码序列.
主要成果:
- 45%的测试保存序列的功能可重现为组织特异增强剂.
- 大多数已识别的增强剂 (75) 将基因表达指向发育中的神经系统,特别是前脑.
- 用前脑准元素丰富的序列签名提高了预测准确性.
结论:
- 进化保护是识别功能性基因增强剂的强大过器.
- 这项研究显著扩大了人体特征增强剂的范围,并提供了有价值的培训数据.
- 这些发现有助于解码人类基因组的调控词汇,并支持各种生物应用.
相关概念视频
Genomic DNA in Eukaryotes
Eukaryotes have large genomes compared to prokaryotes. To fit their genomes into a cell, eukaryotic DNA is packaged extraordinarily tightly inside the nucleus. To achieve this, DNA is tightly wound around proteins called histones, which are packaged into nucleosomes that are joined by linker DNA and coil into chromatin fibers. Additional fibrous proteins further compact the chromatin, which is recognizable as chromosomes during certain phases of cell division.
In-vitro Mutagenesis
To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
Cis-regulatory Sequences
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
Multi-species Conserved Sequences
Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved DNA...
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved DNA...
In vitro Mutagenesis
To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
Cis-regulatory Sequences
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...


