识别非甲基化组合素H3 lysine 4链接BHC80到LSD1-介导的基因抑制
Fei Lan1, Robert E Collins, Rossella De Cegli
1Department of Pathology, Harvard Medical School, 77 Ave Louis Pasteur, Boston, Massachusetts 02115, USA.
Nature
|August 10, 2007
概括
BHC80蛋白特别结合非甲基化组素H3K4,这对LSD1酶在基因抑制中的活性至关重要. 这种相互作用对于维持表观遗传状态和转录调节至关重要.
科学领域:
- 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
- 基因规则 基因规则
背景情况:
- 基因组甲基化调节染色体结构和基因转录.
- 氨酸特异性基因组脱甲酶1 (LSD1) 通过脱甲基化基因组H3.3来抑制转录.
- BHC80 (PHF21A) 是LSD1复合体中的一种蛋白质,其作用尚不清楚.
研究的目的:
- 研究LSD1复合体内BHC80蛋白的功能.
- 为了确定 BHC80 的 PHD 指与 histone H3 的相互作用.
- 阐明BHC80在LSD1介导的转录抑制中的作用.
主要方法:
- 进行X射线晶体学以确定与H3结合的BHC80 PHD指的结构.
- 通过RNA抑制 (RNAi) 来抑制BHC80的表达.
- 野生型和突变型BHC80的重新引入.
- 染色体免疫沉 (ChIP) 评估蛋白质与染色体的关联.
主要成果:
- BHC80的PHD手指特别结合非甲基化H3K4 (H3K4me0),不同于其他结合H3K4me3.3的PHD手指.
- 晶体结构揭示了H3K4me0识别的机制.
- BHC80倒置去抑制的LSD1目标基因.
- BHC80和LSD1在染色体关联方面表现出相互依赖.
结论:
- BHC80将LSD1的功能与未甲基化H3K4.4的识别相结合.
- 未经修改的H3K4被确定为"基因组码"的关键组成部分.
- 识别未经修改的基因组状况可能与基因调节的修改一样重要.
相关概念视频
Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
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...
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...
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...
Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
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...


