由H3K9me2脱甲基化触发的DNA氧化驱动了雌激素诱导的基因表达
Bruno Perillo1, Maria Neve Ombra, Alessandra Bertoni
1Istituto di Scienze dell'Alimentazione, Consiglio Nazionale delle Ricerche (C.N.R.), 83100 Avellino, Italy. perillo@unina.it
概括
基因表达指导的基因基因修饰. 由LSD1驱动的以雌激素受体为目标的H3氨酸9脱甲基化,启动DNA修复途径,使雌激素诱导的转录成为可能.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因法规 基因法规
背景情况:
- 核细胞组组素的N端尾部经历转录至关重要的修改.
- 雌激素受体活性与对雌激素敏感基因的调节有关.
研究的目的:
- 为了研究H3基因素甲基化和脱甲基化如何影响雌激素敏感基因表达.
- 阐明雌激素受体通过染色体修改指导转录的机制.
主要方法:
- 对H3基因素甲基化和脱甲基化模式的分析.
- 研究雌激素受体在染色质曲和RNA聚合酶II招募中的作用.
- 评估LSD1脱甲基酶激活和过氧化生产的影响.
- 观察了8-oxoguanine-DNA glycosylase 1 和topoisomeraseIIbeta.beta 的招募情况.
主要成果:
- 结合雌激素受体诱导染色质曲以促进RNA聚合酶II相互作用.
- 在增强剂和促进剂位点对H3氨酸9的受体向脱甲基化会激活LSD1.1.
- 局部去甲基化产生过氧化,修改DNA并招募修复酶.
- 这些修改引发了转录的基本染色质和DNA构造变化.
结论:
- 雌激素诱导的转录依赖于一种新的机制,涉及受控的DNA损伤和修复.
- 通过LSD1介导的脱甲基化和随后的DNA修复途径对于雌激素响应基因激活至关重要.
相关概念视频
Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Inheritance 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...
Oogenesis
In human women, oogenesis produces one mature egg cell or ovum for every precursor cell that enters meiosis. This process differs in two unique ways from the equivalent procedure of spermatogenesis in males. First, meiotic divisions during oogenesis are asymmetric, meaning that a large oocyte (containing most of the cytoplasm) and minor polar body are produced as a result of meiosis I, and again following meiosis II. Since only oocytes will go on to form embryos if fertilized, this unequal...
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...
Histone 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,...


