通过更高层次的染色质结构调节体质突变
Ursula E Schoeberl1, Johanna Fitz2, Maximilian von der Linde3
1Research Institute of Molecular Pathology (IMP), Campus-Vienna-Biocenter-1, Vienna Biocenter, 1030 Vienna, Austria; Max Perutz Labs, Vienna Biocenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030 Vienna, Austria; University of Vienna, Max Perutz Labs, Department of Biochemistry and Cell Biology, Dr.-Bohr-Gasse 9, 1030 Vienna, Austria.
Molecular cell
|June 28, 2025
概括
针对抗体成熟的体质突变 (SHM) 依赖于免疫球蛋白重链位点 (IGH) 内的多通道枢纽结构. 这个中心保持V区域接近增强剂,使有效的抗体基因多样化.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 身体突变 (SHM) 对于适应性免疫和抗体成熟至关重要.
- SHM涉及免疫球蛋白变量 (V) 区域的突变,由远程增强剂调节.
- 在SHM中3D染色素拓学的作用尚不清楚.
研究的目的:
- 调查3D染色质拓如何影响人类免疫球蛋白重链位点 (IGH) 的SHM.
- 在抗体基因多样化过程中阐明IGH位点的结构组织.
主要方法:
- 利用Tri-C技术测量单个IGH等位基因上的高阶染色体相互作用.
- 分析了切换区域的凝聚素和转录/变异酶对染色质结构和SHM的影响.
主要成果:
- 确定了一个多路枢纽结构,其中IGH V区域与所有增强器相邻.
- 发现凝聚力介导的循环挤出对于IGH转录或枢纽架构来说并不重要.
- 证明了切换区域的转录和突变发生会创建新的循环,而不会损害枢纽完整性或SHM.
结论:
- 抗体成熟发生在一个稳定的多路枢纽内,该枢纽可容纳多个基因增强器循环.
- 不同IGH细分的转录和突变发生在这个结构框架内非竞争性.
- 3D染色质拓,特别是多路枢纽,对于高效的SHM和抗体成熟至关重要.
相关概念视频
Inheritance of Chromatin Structures
6.6K
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...
6.6K
Duplication of Chromatin Structure
6.0K
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...
6.0K
Epigenetic Regulation
3.1K
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...
3.1K
Heterochromatin
14.6K
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...
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...
14.6K
Chromatin Structure Regulates pre-mRNA Processing
7.2K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.2K
Spreading of Chromatin Modifications
8.5K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.5K


