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Hirota T  Lipp JJ  Toh BH  Peters JM 《Nature》2005,438(7071):1176-1180
Histones are subject to numerous post-translational modifications. Some of these 'epigenetic' marks recruit proteins that modulate chromatin structure. For example, heterochromatin protein 1 (HP1) binds to histone H3 when its lysine 9 residue has been tri-methylated by the methyltransferase Suv39h (refs 2-6). During mitosis, H3 is also phosphorylated by the kinase Aurora B. Although H3 phosphorylation is a hallmark of mitosis, its function remains mysterious. It has been proposed that histone phosphorylation controls the binding of proteins to chromatin, but any such mechanisms are unknown. Here we show that antibodies against mitotic chromosomal antigens that are associated with human autoimmune diseases specifically recognize H3 molecules that are modified by both tri-methylation of lysine 9 and phosphorylation of serine 10 (H3K9me3S10ph). The generation of H3K9me3S10ph depends on Suv39h and Aurora B, and occurs at pericentric heterochromatin during mitosis in different eukaryotes. Most HP1 typically dissociates from chromosomes during mitosis, but if phosphorylation of H3 serine 10 is inhibited, HP1 remains chromosome-bound throughout mitosis. H3 phosphorylation by Aurora B is therefore part of a 'methyl/phos switch' mechanism that displaces HP1 and perhaps other proteins from mitotic heterochromatin.  相似文献   

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组蛋白H3第36位赖氨酸的甲基化修饰在染色质上含量丰富,与活跃转录以及DNA损伤修复等重要生理过程相关.H3K36位点可以被一甲基化、二甲基化和三甲基化3种形式修饰,目前已知的负责组蛋白H3K36三甲基化修饰的人源蛋白是SETD2,负责组蛋白H3K36二甲基化修饰的酶包含NSD1、NSD2和NSD3和ASH1L共4名成员.这些H3K36甲基转移酶都具有非常特异的H3K36位点选择性,因此,对调控体内H3K36甲基化修饰的水平和分布十分重要.此外,它们的表达异常与人类的多种疾病相关.因此,解析组蛋白H3K36甲基转移酶识别并修饰组蛋白底物的分子机制,对揭示这些酶参与的表观遗传调控机制及其在体内的生理功能都具有十分重要的意义.早期的研究使得人们对组蛋白H3K36甲基转移酶催化底物的机制有了较深入的认识,但是由于解析的修饰酶与底物复合物的结构较少,对这些酶特异识别组蛋白底物分子机制的认识尚有很多不足.近年来,随着冷冻电镜技术的应用,H3K36甲基转移酶与核小体底物的复合物结构相继取得了突破,极大地推进了人们对这些酶识别并催化组蛋白底物分子机制的认识.本文以这几个组蛋白H3K36甲基转移酶为主要目标,对其分子机制的最新进展进行介绍总结.   相似文献   

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Chromosome 14 is one of five acrocentric chromosomes in the human genome. These chromosomes are characterized by a heterochromatic short arm that contains essentially ribosomal RNA genes, and a euchromatic long arm in which most, if not all, of the protein-coding genes are located. The finished sequence of human chromosome 14 comprises 87,410,661 base pairs, representing 100% of its euchromatic portion, in a single continuous segment covering the entire long arm with no gaps. Two loci of crucial importance for the immune system, as well as more than 60 disease genes, have been localized so far on chromosome 14. We identified 1,050 genes and gene fragments, and 393 pseudogenes. On the basis of comparisons with other vertebrate genomes, we estimate that more than 96% of the chromosome 14 genes have been annotated. From an analysis of the CpG island occurrences, we estimate that 70% of these annotated genes are complete at their 5' end.  相似文献   

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Yin H  Lin H 《Nature》2007,450(7167):304-308
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首先构建酿酒酵母BY4741组蛋白H3第14位赖氨酸突变菌株,该位点突变后则不能被乙酰化.然后通过Western blot检测突变菌株和未突变菌株(对照菌株)的H3K4三甲基化.结果表明,H3K14突变菌株中未检测到H3K4三甲基化,而作为对照的未突变菌株能够检验到H3K4三甲基化修饰.该结果显示酿酒酵母组蛋白H3K14乙酰化能够对H3K4三甲基化产生影响.  相似文献   

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Generation and annotation of the DNA sequences of human chromosomes 2 and 4   总被引:1,自引:0,他引:1  
Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.  相似文献   

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Sequence and analysis of rice chromosome 4   总被引:1,自引:0,他引:1  
Feng Q  Zhang Y  Hao P  Wang S  Fu G  Huang Y  Li Y  Zhu J  Liu Y  Hu X  Jia P  Zhang Y  Zhao Q  Ying K  Yu S  Tang Y  Weng Q  Zhang L  Lu Y  Mu J  Lu Y  Zhang LS  Yu Z  Fan D  Liu X  Lu T  Li C  Wu Y  Sun T  Lei H  Li T  Hu H  Guan J  Wu M  Zhang R  Zhou B  Chen Z  Chen L  Jin Z  Wang R  Yin H  Cai Z  Ren S  Lv G  Gu W  Zhu G  Tu Y  Jia J  Zhang Y  Chen J  Kang H  Chen X  Shao C  Sun Y  Hu Q  Zhang X  Zhang W  Wang L  Ding C  Sheng H  Gu J  Chen S  Ni L  Zhu F  Chen W  Lan L  Lai Y  Cheng Z  Gu M  Jiang J  Li J  Hong G  Xue Y  Han B 《Nature》2002,420(6913):316-320
Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis.  相似文献   

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Global histone acetylation and deacetylation in yeast   总被引:67,自引:0,他引:67  
Vogelauer M  Wu J  Suka N  Grunstein M 《Nature》2000,408(6811):495-498
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