CTCF调节B型肝炎病毒的ccDNA染色素拓结构
Mihaela Olivia Dobrica1,2, Christy Susan Varghese3, James Michael Harris1
1Nuffield Department of Medicine, University of Oxford, Oxford, UK.
The Journal of general virology
|January 4, 2024
概括
CCCTC结合因子 (CTCF) 通过维护染色体结构来调节乙型肝炎病毒 (HBV) 转录. CTCF的枯竭增加了病毒拼接转录,特别是来自病例性ccccDNA的转录,突出了它在HBV基因表达中的作用.
科学领域:
- 病毒学 病毒学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 乙型肝炎病毒 (HBV) 复制,使用环状共闭圆形DNA (cccDNA) 作为模板.
- CCCTC结合因子 (CTCF) 是一种通过表观遗传机制调节细胞转录的宿主蛋白.
- 以前的研究表明,CTCF抑制HBV转录,但机制尚不清楚.
研究的目的:
- 阐明CTCF调节HBV转录的机制.
- 调查CTCF在HBV染色体构成和核细胞定位中的作用.
- 为了确定CTCF规则是否特定于情节性ccDNA.
主要方法:
- 在具有ccDNA类HBV分子和新感染细胞的细胞中CTCF枯竭.
- 病毒转录的分析,包括拼接形式.
- 对转移酶可访问的染色质序列测试 (ATAC-Seq) 的测试,以评估HBV染色质拓.
- 在Enhancer I.中CTCF结合点的突变.
主要成果:
- CTCF 枯竭增加了附接 HBV 转录,特别是 SP1,在具有插曲性 cccDNA 的细胞中.
- CTCF耗尽对集成的HBVDNA没有影响,CTCF结合仅限于集成剂.
- ATAC-Seq揭示了 HBV 增强剂 I/II 和 BCP. 的可访问区域.
- 突变的CTCF位点破坏了染色质的可访问性和核细胞分相.
结论:
- CTCF 调节 HBV 转录,特别是在 插件性 cccDNA 上.
- CTCF维持HBV染色体构造和核细胞定位.
- 在染色质调节中CTCF的作用对于控制HBV基因表达至关重要.
相关概念视频
Inheritance of Chromatin Structures
6.3K
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...
6.3K
Cis-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
Spreading of Chromatin Modifications
8.3K
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...
8.3K
Chromatin Position Affects Gene Expression
23.3K
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
23.3K
Co-activators and Co-repressors
7.4K
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...
7.4K
Heterochromatin
12.9K
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...
12.9K


