不同的因素控制着基因组变异H3.3在特定基因组区域的局部化
Aaron D Goldberg1, Laura A Banaszynski, Kyung-Min Noh
1Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Cell
|March 10, 2010
概括
基因组H3.3变异局部化是由不同的因素引导的,而不仅仅是Hira的陪伴者. 这种表观遗传机制在细胞分化过程中发生变化,影响基因调节和端粒稳定性.
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
- 基因组学就是基因组学.
背景情况:
- 基因组突变,特别是H3.3,在表观遗传记忆和维持细胞状态方面发挥着至关重要的作用.
- 了解H3.3沉积的精确机制对于理解基因调节和分化至关重要.
研究的目的:
- 在哺乳动物胚胎干细胞和神经元前体细胞中绘制全基因组H3.3变异分布图.
- 阐明特定的陪伴者和相关蛋白质在H3.3局部化中的作用,在各种基因组位置.
主要方法:
- 使用指核酶进行基因组编辑以标记内源的H3.3.3.
- 进行全基因组分析,免疫 afinity 净化和质谱.
主要成果:
- H3.3的分布模式依赖于序列,并在细胞分化过程中动态调节.
- 希拉伴侣对H3.3丰富在活跃和抑制的基因中至关重要,但不是在端粒或所有转录因子结合位点上.
- Atrx和Daxx独立于Hira与H3.3结合,Atrx对于H3.3在端粒的定位和端粒RNA抑制至关重要.
结论:
- 多种不同的蛋白质因子将H3.3定位到特定的基因组区域.
- 细胞分化涉及H3.3变异分布的动态表观遗传重编程.
相关概念视频
02:30Histone Variants at the Centromere
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3 variants are also...
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,...
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,...
02:32Position-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.
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...
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...