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H2AZ在ES细胞中的多复合基因中富含,对于血统承诺是必要的
Menno P Creyghton1, Styliani Markoulaki, Stuart S Levine
1Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Cell
|November 11, 2008
概括
基因组变异H2AZ对哺乳动物发育至关重要,它与Polycomb组蛋白一起调节基因表达和细胞分化. 它的动态再分配是细胞命运过渡的关键.
科学领域:
- 表观遗传学和发育生物学
- 染色体生物学 染色体生物学
- 基因规则 基因规则
背景情况:
- 染色体结构显著影响基因表达和细胞命运的决定.
- 基因素变体H2AZ与染色质功能有关,在哺乳动物发育中发挥着关键但未定义的作用.
研究的目的:
- 研究H2AZ在哺乳动物发育中的作用及其与多组 (PcG) 蛋白质的关系.
- 阐明H2AZ如何影响发育过程中的基因表达和细胞分化.
主要方法:
- 全基因组分析,绘制基因促进者的H2AZ占用率.
- RNA干扰 (RNAi) 来评估H2AZ对基因表达的功能影响.
- 对H2AZ和PcG蛋白在基因促进体中的相互依赖性进行分析.
主要成果:
- H2AZ占据了发育重要基因的促进者,类似于PcG蛋白Suz12.
- H2AZ对于调节基因表达至关重要,并且与促进体中的PcG蛋白相互依赖.
- H2AZ对于胚胎干细胞 (ES) 的分化是必需的,并且在血统承诺的细胞中动态重新分配.
结论:
- H2AZ与PcG蛋白结合,在ES细胞中建立了专门的染色质状态.
- H2AZ的动态再分配对于执行发育基因表达程序和促进细胞命运过渡至关重要.
相关概念视频
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.
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...
Lineage Commitment
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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...
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Maintenance of the ES Cell State
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
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...

