MLL1 PHD3-ブロモカセットにおけるプロイソメリゼーションは,H3K4meの読み出しをCyP33とHDAC媒介による抑圧と接続する
Zhanxin Wang1, Jikui Song, Thomas A Milne
1Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Cell
|June 15, 2010
まとめ
MLL1遺伝子である.
科学分野:
- 分子生物学は分子生物学である.
- エピジェネティクス エピジェネティクス
- がん研究 がん研究
背景:
- MLL1遺伝子は,白血病につながる染色体転位に頻繁に関与しています.
- MLL1の規制メカニズムを理解することは,白血病の幹細胞生物学にとって極めて重要です.
研究 の 目的:
- MLL1がヒストンマークとサイクロフィリンCyP33.3に結合する分子メカニズムを解明する.
- MLL1の機能と遺伝子抑制の調節におけるCyP33の役割を調査する.
主な方法:
- MLL1,ヒストーンH3K4me3/2,およびサイクロフィリンCyP33.3の構造機能研究.
- タンパク質とタンパク質の相互作用とドメイン機能の分析 (PPIase,RRM,PHD3-Bromo).
- HOXA9とHOXC8.8のインビボ遺伝子抑制アッセイについて
主要な成果:
- CyP33のPPIaseドメインは,プロリンイソメリゼーション経由でMLL1構成を調節し,PHD3-ブロモインターフェースを破壊する.
- MLL1-PHD3ドメインはH3K4me3/2とCyP33-RRMに同時に結合し,三元複合体を形成する.
- MLL1-CyP33の相互作用は,HOXA9とHOXC8の遺伝子発現を vivo で抑制するために不可欠です.
結論:
- MLL1 PHD3-Bromoカセットは,規制プラットフォームとして機能します.
- このプラットフォームは,MLL1がH3K4me3 / 2マークと相互作用し,HDACの採用を通じてCyP33による抑圧をオーケストラします.
関連する概念動画
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
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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...


