胚胎DNA甲基化计划对CTCF介导的基因组调节的影响
Ana Monteagudo-Sánchez1, Julien Richard Albert1, Margherita Scarpa1
1Université Paris Cité, CNRS, Institut Jacques Monod, F-75013 Paris, France.
Nucleic acids research
|August 24, 2024
概括
在胚胎发育过程中,DNA甲基化 (5meC) 动态影响3D基因组架构. 这项研究揭示了5meC如何对抗CTCF结合,影响染色体折叠和基因调节.
科学领域:
- 表观遗传学和发育生物学
- 基因组学和染色体结构
背景情况:
- 哺乳动物胚胎生成涉及DNA甲基化 (5meC) 和3D染色体结构的显著重塑.
- 5meC动态和3D基因组组织之间的相互作用,特别是CTCF结合,仍然没有得到充分的研究.
研究的目的:
- 为了研究5 - 细胞因子DNA甲基化 (5meC) 流程如何在表观遗传重编程期间影响3D基因组.
- 确定5meC对CTCF结合的影响及其在染色体折叠和基因调节中的作用.
主要方法:
- 使用小鼠胚胎干细胞 (ESC) 差异化模型,有或没有DNA甲基化机制.
- 执行了CTCF HiChIP和H3K27ac HiChIP以分析染色体接触.
- 采用5meC表观基因组编辑来评估甲基化对CTCF结合的影响.
主要成果:
- 证明5meC可以损害特定基因组位置的CTCF结合.
- 在没有5meC的情况下识别了获得的CTCF-CTCF联系人.
- 展示了5meC-CTCF对抗性如何在分化过程中促进zdbf2位点的基因调节.
结论:
- 5meC通过影响CTCF结合,在调节3D基因组架构方面发挥着至关重要的作用.
- 这种对抗性对于哺乳动物胚胎发育过程中适当的基因调节至关重要.
相关概念视频
Epigenetic Regulation
3.0K
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...
3.0K
Genomic Imprinting and Inheritance
34.2K
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
34.2K
Chromatin Modification in iPS Cells
1.6K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.6K
Methods of Nuclear Reprogramming
1.8K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
1.8K
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
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


