在DNA分子中将甲基细胞氨酸与基甲基细胞氨酸区分开来
Meni Wanunu1, Devora Cohen-Karni, Robert R Johnson
1Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States. wanunu@sas.upenn.edu
Journal of the American Chemical Society
|December 16, 2010
概括
本研究介绍了一种物理方法,以区分5-甲基细胞因子 (mC) 和5-基甲基细胞因子 (hmC) 的DNA修饰. 固态纳米孔可以快速区分这些表观遗传标记,有助于疾病研究.
科学领域:
- 表观遗传学和分子生物学
- 生物物理学的生物物理.
- 纳米技术纳米技术
背景情况:
- 修改后的DNA基,包括5-甲基氨酸 (mC),是真核生物中关键的表观遗传标记.
- 5-基甲基细胞素 (hmC) 是一种最近在哺乳动物细胞中发现的已识别的修饰物.
- 目前的测试很难在DNA片段中区分mC和hMC.
研究的目的:
- 为了研究含有mC和hMC修饰的DNA的物理性质.
- 开发一种能够在DNA片段中区分mC和hMC的物理工具.
- 为了准确量化生物样本中的hmC比例.
主要方法:
- 模拟分子动力学以分析内部基对动力学.
- 实验调查细胞因子修饰极性,DNA灵活性和双重稳定性之间的相关性.
- 固态纳米孔技术用于根据物理性质区分DNA片段.
主要成果:
- 发现极地细胞因子的修改会影响内部基对动态.
- 细胞因子修饰极性,DNA灵活性和双重稳定性之间存在相关性.
- 固态纳米孔成功地区分了mC和hMC修饰的DNA片段.
- 来自纳米孔分析的电子签名允许确定hmC的相对比例.
结论:
- 具有mC和hMC修饰的DNA的物理差异可以被利用进行歧视.
- 固态纳米孔技术提供了一种快速有效的方法来区分和量化这些表观遗传标记.
- 这种方法在理解基因调节,发育,衰老,癌症和疾病方面具有潜在的应用.
相关概念视频
Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Heterochromatin
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...
Mismatch Repair
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
Mismatch Repair
Overview
Phase II Reactions: Methylation Reactions
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...


