活细胞中色素的动力学和记忆
Nathaniel A Hathaway1, Oliver Bell, Courtney Hodges
1Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell
|June 19, 2012
概括
这项研究揭示了像H3K9me3这样的基因组修饰如何在细胞代中传播和遗传. 这些表观遗传标记形成稳定的领域,影响基因表达和细胞记忆.
科学领域:
- 表观遗传学和基因调控
- 染色体生物学 染色体生物学
- 分子细胞生物学 分子细胞生物学
背景情况:
- 翻译后的组织蛋白修饰在基因调节中起着至关重要的作用.
- 这些修饰在维持基因表达状态中的传播和遗传机制尚未完全理解.
研究的目的:
- 为了研究活细胞中染色质修饰的动态和遗传性.
- 量化建模控制异色域形成和稳定的动力学.
主要方法:
- 开发一种使用化学诱导近距离的体内染色体检测 (CiA) 系统.
- 选择性地招募HP1α以诱导H3K9me3依赖基因在Oct4位点的沉默.
- 在纤维细胞和多能细胞中分析染色质修饰动力学.
主要成果:
- H3K9me3的修饰以~0.18核细胞/小时的速度对称且连续地传播,形成高达10kB的域.
- 诱导的异色域在刺激被移除后,在多个细胞代中稳定地继承.
- 定量建模揭示了质子标记和周转动态决定了域稳定性和边界.
结论:
- 这项研究为了解异色染色体域形成和稳定性提供了定量框架.
- 基因组修饰和转换之间的动态竞争决定了表观遗传.
- 这个模型预测了整个基因组的H3K9me3域的行为.
相关概念视频
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...
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...
Inheritance of Chromatin Structures
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
Euchromatin
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...
Duplication of Chromatin Structure
The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
Position-effect Variegation
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.


