UpSET招募HDAC复合体,并限制促进区域的染色质可访问性和乙化
Hector Rincon-Arano1, Jessica Halow, Jeffrey J Delrow
1Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Cell
|November 27, 2012
概括
该研究确定了upsET,drosophila中的转录调节剂,可以防止活性染色体标记的传播. 它的缺失导致转录噪声增加和女性不育.
科学领域:
- 表观遗传学和基因调控
- 发展生物学 发展生物学
- 染色体生物学 染色体生物学
背景情况:
- 发育性基因表达依赖于遗传和表观遗传相互作用.
- 众所周知,SET域蛋白是转录的调节者.
- 该Rpd3/Sin3复合体参与了基因素脱乙烯化.
研究的目的:
- 描述 upSET,一种新的 SET 域含有 Drosophila. 的转录调节器.
- 研究upSET在染色质可访问性和基因表达中的作用.
- 了解upSET在女性生殖和女性生育中的作用.
主要方法:
- 在Drosophila中识别和表征upSET基因和蛋白质.
- 在野生型和上SET突变中分析染色质可访问性和基因素乙化模式.
- 对基因表达的评估,包括转录噪声和重复元素激活.
- 在upSET突变体中 oogenesis 期间检查 Notch 信号通路组件.
主要成果:
- UpSET是一种转录调节器,被招募到活跃的基因中,在Rpd3/Sin3复合体内运行.
- UpSET限制了染色质可访问性和基因素乙化到促进器区域.
- upSET的丧失导致染色体可访问性增加,活性标记扩散到基因和侧面区域.
- 缺少upSET会导致转录噪声增加,重复元素的激活,以及异位基因表达.
- 在upSET突变中,由于 oogenesis 过程中 Notch 信号组件的上调,导致雌性不育.
结论:
- UpSET定义了一类新型的甲动物转录调节器.
- UpSET对于微调转录是必不可少的,因为它限制了活性染色体的传播.
- 上升SET功能的失调会影响染色体组织,基因表达忠实性和生殖发育.
相关概念视频
02:54Nucleosome Remodeling
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
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Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
02:32Histone 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
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02:25Spreading 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...
02:38Heterochromatin
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...
02:32Histone 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,...
01:32Chromatin Modification in iPS Cells
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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...