在carboxy终端域内的负电荷区域保持了适当的CTCFDNA结合
Lian Liu1, Yuanxiao Tang1, Yan Zhang1
1Center for Comparative Biomedicine, Ministry of Education Key Laboratory of Systems Biomedicine, State Key Laboratory of Medical Genomics, Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
iScience
|December 25, 2024
概括
CCCTC结合因子 (CTCF) 的C端域调节其DNA结合. 这个域内的特定区域削弱了结合,影响了基因调节和3D基因组组织.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 蛋白质结构和功能 蛋白质结构和功能
背景情况:
- CCCTC-结合因子 (CTCF) 对高阶染色体结构至关重要.
- CTCF是一种保存的蛋白质,具有具有指 (ZF) 和内在无序的N-和C-终端域的DNA结合域.
研究的目的:
- 研究CTCF的C端域在DNA结合和基因调节中的作用.
- 在C端域内确定调节CTCF功能的特定区域.
主要方法:
- 用CRISPR基因编辑进行域删除.
- 电泳运动转移试验 (EMSA) 用于DNA结合.
- 4C,ChIP-seq和ATAC-seq用于全基因组分析.
- 对于结构洞察的AlphaFold预测.
主要成果:
- 删除整个C端域减少了CTCFDNA结合.
- 删除特定的116-氨基酸片段增加了CTCFDNA结合,并导致异常基因调节.
- 一个负电荷区域 (NCR) 被确定为削弱CTCFDNA结合和染色质可访问性.
结论:
- CTCF的C端域在调节其DNA相互作用方面发挥着关键的,复杂的作用.
- 涉及NCR的自身抑制机制可能控制CTCFDNA结合和3D基因组组织.
相关概念视频
Chromatin Position Affects Gene Expression
23.1K
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...
23.1K
Conserved Binding Sites
4.1K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.1K
Cis-regulatory Sequences
9.5K
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...
9.5K
Catenins
2.2K
Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
2.2K
Heterochromatin
9.0K
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...
9.0K
Co-activators and Co-repressors
7.1K
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...
7.1K


