活跃的调节元素招募凝聚力,以建立细胞特异性染色质域
Emily Georgiades1, Caroline Harrold1, Nigel Roberts1
1MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Scientific reports
|April 6, 2025
概括
活性增强剂招募凝聚力,驱动细胞类型特定的基因组架构. 这一过程形成了新的基因组结构,称为子TADs,对基因调节和细胞身份至关重要.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 三维基因组结构在不同细胞类型之间存在显著差异.
- 细胞类型特定的染色体结构可能来自于凝聚性对cis-regulatory元素的招募.
- 这种招聘可以推动循环挤出,并形成新的子TAD.
研究的目的:
- 研究活性增强剂在招募凝聚力中的作用.
- 为了确定增强剂的存在是否影响等位基特异性染色体结构.
- 阐明细胞类型特异性亚TAD形成的机制.
主要方法:
- 在高分辨率下分析3D基因组架构.
- 凝聚素结合和活性增强剂之间的相关性研究.
- 在阿尔法环球蛋白集群模型中对增强剂的实验操纵.
- 增强元件的全基因组插入实验.
主要成果:
- 凝聚素水平与活性增强剂的存在有很强的相关性,显示出异位基因特异性的变化.
- 移除增强剂消除了凝聚素峰值和红色素特异性亚TAD形成.
- 重新插入增强剂恢复了凝聚力招募和相互作用.
- 将增强剂插入中性部位诱导转录,并形成一个新的红状腺特异性域.
结论:
- 活性增强剂是凝聚力招募的关键驱动力.
- 通过增强剂的凝聚素招募刺激了循环挤出.
- 这种机制促进了细胞类型特定的子TADs的形成,塑造了3D基因组组织.
相关概念视频
Inheritance of Chromatin Structures
6.2K
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...
6.2K
Heterochromatin
9.1K
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...
9.1K
Spreading of Chromatin Modifications
8.1K
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...
8.1K
Cohesins
4.3K
Cohesin protein complexes are a molecular glue that holds two sister chromatids together. They play an important role both in mitosis and meiosis. In mitosis, all cohesin complexes present on the chromosomes are removed before the start of the anaphase stage.
Cohesin complexes in Meiotic Division
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of...
Cohesin complexes in Meiotic Division
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of...
4.3K
Duplication of Chromatin Structure
5.3K
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...
5.3K
Co-activators and Co-repressors
7.2K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.2K


