在活动依赖的BDNF基因调节中,与DNA甲基化相关的染色质重塑
Keri Martinowich1, Daisuke Hattori, Hao Wu
1Neuroscience Interdepartmental Program, UCLA School of Medicine, 760 Westwood Plaza, Los Angeles, CA 90095, USA.
Science (New York, N.Y.)
|November 1, 2003
概括
DNA甲基化和染色质重塑对于基因沉默至关重要. 大脑衍生神经营养因子 (BDNF) 基因促进体中DNA甲基化减少会增强其转录,影响神经可塑性.
科学领域:
- 神经科学是一个神经科学.
- 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.
背景情况:
- 基因甲基化和基因组修饰是通过染色质重塑调节基因表达的关键表观遗传机制.
- DNA甲基化模式的改变可以破坏神经元功能,甲基-CpG结合蛋白2 (MeCP2) 的突变与雷特综合征有关.
研究的目的:
- 研究DNA甲基化在神经元中活动依赖基因调节中的作用.
- 探索神经元脱极化,BDNF基因表达和DNA甲基化动态之间的关系.
主要方法:
- 在神经元脱极化后,Bdnf基因调节区域内分析CpG甲基化水平.
- 从Bdnf促进体中评估MeCP2-素脱乙酶-mSin3A复合物的解离.
主要成果:
- 神经元脱极化与Bdnf基因调节区CpG甲基化降低相关.
- 增加的Bdnf转录与MeCP2抑制剂复合体与基因促进体的解离有关.
结论:
- 以DNA甲基化为媒介的染色质重塑对于神经元中活动依赖基因调节至关重要.
- 这些发现强调了表观遗传机制在神经可塑性和功能中的重要性.
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...
02:32Position-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.
02:32Histone 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,...
01:02Long-patch Base Excision Repair
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
02:08Gene Conversion
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
01:32Chromatin 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...