人类基因组的可访问的染色质景观
Robert E Thurman1, Eric Rynes, Richard Humbert
1Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
Nature
|September 8, 2012
概括
我们绘制了数百万个DNAse I过敏位点 (DHS),揭示了新的调节性DNA元素及其细胞特异性功能. 这张地图将监管区域与促进者联系起来,并揭示了染色质可访问性和人类遗传变异之间的联系.
科学领域:
- 基因组学就是基因组学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 调控生物学 调控生物学
背景情况:
- DNAse I 过敏位点 (DHS) 是调控DNA的关键标记物,可以识别增强剂和促进剂等元素.
- 之前的研究已经绘制了DHS,但缺乏跨多种人类细胞类型的全面的全基因组地图.
研究的目的:
- 创建第一个广泛的基因组全方位地图的人类DHS在125个不同的细胞和组织类型.
- 识别新的调节元素,了解它们的细胞选择性调节和功能关系.
主要方法:
- 全基因组分析以识别125种人类细胞和组织类型的DHS.
- 使用ENCODE数据进行注释,分析染色质可访问性,转录,DNA甲基化和调控因子占用之间的关系.
- 计算分析将远程DHS与目标促进体连接起来,并识别协同激活的元素.
主要成果:
- 确定了大约290万个DHS,覆盖了已知的调节序列,并揭示了许多新的细胞选择性元素.
- 建立了染色质可访问性,转录,DNA甲基化和调控因子结合之间的新联系.
- 连接了大约58万个远程DHS与它们的目标促进体,揭示了系统的配对和协同激活元素的有组织模式.
- 证明DHS模式预测细胞类型特定的功能,并确定了多能细胞中的DHS,突变率和人类变异之间的联系.
结论:
- 综合的DHS地图提供了一个丰富的资源,用于发现和理解cis-regulatory元素及其功能.
- 染色体可访问性模式是有组织的,可以预测细胞功能,对人类遗传变异和进化有影响.
相关概念视频
02:35Chromatin Position Affects Gene Expression
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of...
01:01Euchromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
01:01Euchromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
01:32Chromatin Packaging
Each human somatic cell contains 6 billion base pairs of DNA. Each base pair is 0.34 nm long, meaning each diploid cell contains a staggering 2 meters of DNA. This long DNA strand is packed inside a nucleus measuring only 10-20 microns in diameter with the help of specialized DNA-binding proteins called histones. Together they form a compact DNA-protein complex called chromatin. The chromatin is further compacted into higher-order structures. The highest level of compaction is achieved during...