在HP1中,一个构造性开关释放自我抑制以驱动异色染色体组件
Daniele Canzio1, Maofu Liao, Nariman Naber
1Department of Biochemistry and Biophysics, University of California San Francisco, California 94158, USA.
Nature
|March 15, 2013
概括
与甲基化核酶结合的异位染色蛋白1 (HP1) 将Swi6从自抑制状态转换为具有传播能力的状态,这对于基因沉默和异位染色蛋白组装至关重要.
科学领域:
- 染色体生物学 染色体生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因调节的分子机制
背景情况:
- 基因组H3氨酸9 (H3K9) 甲基化 heterochromatin 扩散到相邻的区域,涉及 heterochromatin 蛋白 1 (HP1).
- 惠普1识别了H3K9甲基化染色质,并形成基因沉默和染色体分离的平台.
- HP1在甲基化核细胞体上的组合及其功能多功能性尚未得到充分理解.
研究的目的:
- 为了阐明HP1蛋白如何在甲基化核酶模板上组装.
- 了解HP1-核酶体复杂的功能多功能性背后的机制.
- 为了研究Swi6 (HP1) 与甲基化核子体结合的自抑制到传播能力的状态切换.
主要方法:
- 基于冷电子显微镜的Swi6核体复合体的重建.
- 在体内研究以评估破坏自抑制/扩散能力状态开关的影响.
主要成果:
- Swi6与甲基化核酶的结合触发了从自抑制状态到扩散能力状态的切换.
- 在自抑制状态下,一个基因素模仿序列阻止了染色体甲基标记的识别.
- 自动抑制通过识别H3K9甲基标记和核细胞DNA来缓解,暴露"粘性末端"以传播.
- 这种开关的中断会损害体内异性染色质组合和基因沉默.
结论:
- HP1-核酶相互作用涉及条件激活机制,在自抑制和传播能力之间切换.
- 这种开关通过识别H3K9甲基标记和核细胞DNA来调节.
- 这些发现揭示了染色体扩散和基因沉默的新型调节机制.
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
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
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...
03:17Inheritance of Chromatin Structures
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
01:01Euchromatin
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...
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...
02:38Heterochromatin
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...