在MLL1 PHD3-bromo磁带中的pro isomerization将H3K4me读数连接到CyP33和HDAC介导的抑制
Zhanxin Wang1, Jikui Song, Thomas A Milne
1Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Cell
|June 15, 2010
概括
这就是MLL1基因.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症研究 癌症研究
背景情况:
- MLL1基因经常参与导致白血病的染色体转位.
- 了解MLL1的调节机制对于白血病干细胞生物学至关重要.
研究的目的:
- 阐明MLL1结合基因素标记和环素CyP33.3的分子机制.
- 研究CyP33在调节MLL1功能和基因抑制中的作用.
主要方法:
- 对MLL1,基因素H3K4me3 / 2和环菲林CyP33.3的结构功能研究.
- 蛋白质与蛋白质相互作用和域功能 (PPIase,RRM,PHD3-Bromo) 的分析.
- 在体内对HOXA9和HOXC8.8进行基因抑制试验.
主要成果:
- CyP33 的 PPIase 域通过林异构化调节 MLL1 构造,破坏 PHD3-Bromo 接口.
- MLL1-PHD3域与H3K4me3/2和CyP33-RRM同时结合,形成一个三元复合体.
- 在体内抑制HOXA9和HOXC8基因表达时,MLL1-CyP33相互作用至关重要.
结论:
- MLL1 PHD3-Bromo磁带作为一个监管平台.
- 这个平台通过HDAC招募协调MLL1与H3K4me3/2标志的互动以及CyP33介导的镇压.
相关概念视频
Heterochromatin
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 9th...
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 9th...
Euchromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Position-effect Variegation
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.
Spreading of Chromatin Modifications
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 is an enzyme that can...
Writers
The writer is an enzyme that can...
Chromatin Modification in iPS Cells
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...
Eukaryotic Transcription Inhibitors
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...


