组织素H3氨酸27甲基化在Polycomb组沉默中的作用
Ru Cao1, Liangjun Wang, Hengbin Wang
1Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
概括
这项研究确定了基因组甲基化和Polycomb组 (PcG) 蛋白质介导基因沉默之间的直接联系. EED-EZH2复合物在氨酸27处甲基化素H3,这是维持基因沉默的关键步骤.
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
- 基因法规 基因法规
背景情况:
- 多组 (PcG) 蛋白质对于保持HOX基因的静态状态至关重要.
- 基因组甲基化已与长期的基因沉默有关.
- 此前,PcG介导的沉默和基因组甲基化之间的直接联系尚未确立.
研究的目的:
- 为了研究将Polycomb组蛋白和基因素甲基化联系在一起的分子机制.
- 描述虫ESC-E(Z) 复合物的人类对应物及其酶活性.
- 建立基因组甲基化和PCG介导的基因沉默之间的直接联系.
主要方法:
- 人类EED-EZH2复合物的净化和表征.
- 测试以确定该复合体的组胺甲基转移酶活性.
- 染色体免疫沉 (ChIP) 试验在体内评估H3-K27甲基化和E(Z) 结合.
- 分析H3-K27甲基化与基因抑制之间的相关性.
主要成果:
- 净化了EED-EZH2复合体,并将其描述为人类的ESC-E(Z) 对应物.
- 综合体被证明可以在lysine 27 (H3-K27) 处特异地甲基化核细胞组组质组蛋白H3.
- 发现H3-K27甲基化与E(Z) 结合在Ultrabithorax (Ubx) 聚合体反应元件 (PRE) 的同位体并依赖于E(Z) 结合,与Ubx抑制相关.
- 已经证明,H3-K27的甲基化有助于Polycomb (PC) 蛋白 (PRC1的组成部分) 与H3氨基终端尾 histone的结合.
结论:
- 这些发现确定了基因组甲基化和Polycomb组介导的基因沉默之间的直接机械联系.
- 由EED-EZH2复合体进行的Histon H3 lysine 27甲基化是PcG介导的基因抑制的关键表观遗传标记.
- 这种甲基化事件作为一个平台来招募其他PCG组件,如PRC1.1.
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.
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...
Combinatorial Gene Control
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
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...
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...


