针对SETDB1的细胞类型差异向可以防止异常的CTCF结合,染色质循环和cis调节相互作用
Phoebe Lut Fei Tam1, Ming Fung Cheung1,2, Lu Yan Chan1,2
1Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, SAR, China.
Nature communications
|January 3, 2024
概括
通过SETDB1介导的H3K9me3标记可以防止异常的CTCF结合,从而保持细胞的身份. 这种表观遗传调节通过调节色素循环来塑造基因组架构和基因表达.
科学领域:
- 表观遗传学和基因组学
- 分子生物学分子生物学
- 染色体生物学 染色体生物学
背景情况:
- SETDB1是一个关键的基因组甲基转移酶,用于基因抑制,沉积H3K9me3.
- 细胞类型特定的H3K9me3丰富的作用尚不清楚.
- CTCF是一种关键的蛋白质,参与基因组组织.
研究的目的:
- 调查SETDB1,H3K9me3和CTCF之间的功能关系.
- 了解SETDB1介导的H3K9me3如何影响高阶基因组架构和转录.
- 阐明SETDB1在维持细胞身份中的作用.
主要方法:
- 在小鼠组织中分析H3K9me3和CTCF占用率.
- 在细胞中SETDB1耗尽实验.
- 用于表观遗传分析的CHIP-seq和ATAC-seq.
- 3D基因组架构分析 (Hi-C).
- 转录基因分析 (RNA-seq).
主要成果:
- 在小鼠组织中,H3K9me3和CTCF结合是相互排斥的.
- SETDB1 枯竭导致异常的 CTCF 结合在 SINE B2 逆转移素丰富区域,独立于 DNA 甲基化和 H3K9me2.
- 虽然大型染色体结构 (TAD,隔间) 保持完整,但染色体循环和局部3D相互作用在SETDB1耗尽时被破坏.
- 破坏的相互作用与改变的基因表达和失调的cis-regulatory元素相关.
- 通过调节CTCF结合和塑造核架构,SETDB1目标对于保持细胞身份至关重要.
结论:
- 通过SETDB1介导的H3K9me3在防止异常CTCF结合方面发挥着关键作用,从而保护基因组组织和基因表达.
- 这种表观遗传机制对于维持细胞类型特异性身份至关重要.
- 通过调节CTCF结合点,SETDB1的功能影响了局部染色体相互作用和更广泛的转录组网络.
相关概念视频
02:23Master 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
01:19Cadherins in Tissue Organization
3.0K
The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell Sorting During Development
Cell sorting plays an...
3.0K
02:02Cis-regulatory Sequences
9.9K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
9.9K
01:30General Transcription Factors
5.3K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
5.3K
02:13Cooperative Binding of Transcription Regulators
6.4K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
6.4K
02:16Transcription Factors
75.9K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
75.9K