关于JMJD2家族成员对基因素脱甲基化的结构见解
Zhongzhou Chen1, Jianye Zang, Johnathan Whetstine
1Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Cell
|May 9, 2006
概括
研究人员确定了JMJD2A基因脱甲基酶核心域的结构. 这种结构洞察力为JMJD2基因组脱甲基酶如何选择它们的基质提供了一个分子模型.
科学领域:
- 生物化学 生物化学
- 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:
- 基因组的翻译后修改对于调节染色质结构和基因表达至关重要.
- 基因组脱甲基酶是一种新型的转录因子,它从基因组 lysine 残留物中去除甲基,从而影响基因转录.
- 含有JmjC域的蛋白质被认为是基因组脱甲基酶,JMJD2A被确定为H3-K9me3和H3-K36me3.3的特异性.
研究的目的:
- 阐明JMJD2A基因组脱甲基酶活性的结构基础.
- 了解JMJD2家族中基质选择的基础分子机制.
主要方法:
- 采用X射线晶体学来确定JMJD2A催化核域的结构.
- 在Fe2+的存在下,在含有或不含α-甲酸的情况下获得了结构.
- 进行了局部定向突变发生和脱甲基酶活性测试.
主要成果:
- 确定了JMJD2A催化核域的晶体结构,包括JmjN,JmjC,C端域和一个指图案.
- 确定了形成潜在基质结合口袋的独特结构元素.
- 基于突变发生和活性数据,提出了一个由JMJD2基因组脱甲基酶家族选择基质的分子模型.
结论:
- 确定的结构为JMJD2A.的催化机制提供了关键的见解.
- 这些发现有助于更深入地了解表观遗传调节中的基因组脱甲基酶功能.
- 拟议的模型有助于理解JMJD2基因组脱甲基酶家族内的基质特异性.
相关概念视频
02:10The Nucleosome Core Particle
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
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,...
02:25Spreading 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...
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,...
01:12The Nucleosome Core Particle
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...