作为DIM2介导的DNA甲基化开关的多层异位染色素相互作用
Zengyu Shao1, Jiuwei Lu1, Nelli Khudaverdyan1
1Department of Biochemistry, University of California, Riverside, CA, 92521, USA.
Nature communications
|August 9, 2024
概括
这项研究揭示了DNA甲基转移酶DIM2如何使用基因素修饰 (H3K9me3) 和HP1蛋白来实现特定的DNA甲基化,与哺乳动物酶不同.
科学领域:
- 表观遗传学和染色体生物学
- DNA甲基化分子机制的分子机制
- 基因组稳定性 基因组稳定性
背景情况:
- 在DNA甲基化,H3K9me3和HP1之间的功能交叉对异色染色素组装和基因组稳定性至关重要.
- 通过抑制色素线索引导DNA甲基转移酶到特定的基因组区域的机制尚不清楚.
研究的目的:
- 描述神经中的DNA甲基转移酶DIM2的结构功能.
- 阐明DIM2如何与H3K9me3和HP1相互作用以调节DNA甲基化.
- 与哺乳动物DNMT1.1相比,揭示DIM2的独特基质结合机制.
主要方法:
- DIM2.2的结构功能表征.
- 进行X射线晶体学以确定DIM2-HP1和DIM2-HP1-H3K9me3-DNA复合物的结构.
- 生物化学测试以评估DNA甲基化活性和基质结合.
主要成果:
- DIM2 DNA甲基化活动严格要求H3K9me3和HP1.1.
- 一个双重的DIM2-HP1相互作用会诱导DIM2的目标识别领域的障碍到秩序的过渡,从而使基质结合.
- DIM2-HP1-H3K9me3-DNA复杂结构揭示了一个独特的基质结合机制.
- 通过DIM2的RFTS和BAH1域对H3K9me3的双重识别可全质调节DIM2基质结合和甲基化活性.
结论:
- 多个异色素因子 (H3K9me3,HP1) 协调控制DIM2活动.
- DIM2采用了一种新的区域特异性DNA甲基化机制,与哺乳动物的ortologues不同.
- 这项研究提供了对异性染色质形成和基因组稳定性调节的见解.
相关概念视频
Heterochromatin
11.9K
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...
11.9K
Position-effect Variegation
6.3K
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
6.3K
Spreading of Chromatin Modifications
8.2K
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...
8.2K
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
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
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


