Identification of Histone Mutants That Are Defective for Transcription-Coupled Nucleosome Occupancy

Sarah J. Hainer; Joseph A. Martens

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Identification of Histone Mutants That Are Defective for Transcription-Coupled Nucleosome Occupancy

机译：识别与转录偶联核小体存在缺陷的组蛋白突变体

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Our previous studies of Saccharomyces cerevisiae described a gene repression mechanism where the transcription of intergenic noncoding DNA (ncDNA) (SRG1) assembles nucleosomes across the promoter of the adjacent SER3 gene that interfere with the binding of transcription factors. To investigate the role of histones in this mechanism, we screened a comprehensive library of histone H3 and H4 mutants for those that derepress SER3. We identified mutations altering eight histone residues (H3 residues V46, R49, V117, Q120, and K122 and H4 residues R36, I46, and S47) that strongly increase SER3 expression without reducing the transcription of the intergenic SRG1 ncDNA. We detected reduced nucleosome occupancy across SRG1 in these mutants to degrees that correlate well with the level of SER3 derepression. The histone chromatin immunoprecipitation experiments on several other genes suggest that the loss of nucleosomes in these mutants is specific to highly transcribed regions. Interestingly, two of these histone mutants, H3 R49A and H3 V46A, reduce Set2-dependent methylation of lysine 36 of histone H3 and allow transcription initiation from cryptic intragenic promoters. Taken together, our data identify a new class of histone mutants that is defective for transcription-dependent nucleosome occupancy.

机译：我们以前对酿酒酵母的研究描述了一种基因抑制机制，其中基因间非编码DNA（ncDNA）（ SRG1 ）的转录使核小体跨相邻的 SER3 基因启动子组装。与转录因子的结合。为了研究组蛋白在该机制中的作用，我们筛选了一个完整的组蛋白H3和H4突变体文库，用于寻找抑制 SER3 的蛋白。我们发现了可改变八个组蛋白残基的突变（H3残基V46，R49，V117，Q120和K122残基以及H4残基R36，I46和S47），这些突变可在不减少基因组< em> SRG1 ncDNA。我们检测到这些突变体中跨 SRG1 的核小体占有率降低到与 SER3 抑制水平相关的程度。在其他几个基因上的组蛋白染色质免疫沉淀实验表明，这些突变体中核小体的丢失对高度转录的区域具有特异性。有趣的是，这些组蛋白突变体中的两个H3 R49A和H3 V46A降低了组蛋白H3赖氨酸36的Set2依赖性甲基化，并允许从隐性基因内启动子启动转录。综上所述，我们的数据确定了一类新的组蛋白突变体，其对于依赖转录的核小体占据是有缺陷的。 展开▼

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《Molecular and Cellular Biology》 |2011年第17期|共12页

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Sarah J. Hainer; Joseph A. Martens;
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中图分类细胞生物学;

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1. Identification of Mutant Versions of the Spt16 Histone Chaperone That Are Defective for Transcription-Coupled Nucleosome Occupancy in Saccharomyces cerevisiae [J] . Brittany A. Charsar, Joseph A. Martens, Sarah J. Hainer, G3: Genes, Genomes, Genetics . 2012,第5期

机译：突变体版本的Spt16组蛋白伴侣的转录酵母核糖体占用中缺陷的鉴定。

2. Genome-Wide Analysis of Nucleosome Positions, Occupancy, and Accessibility in Yeast: Nucleosome Mapping, High-Resolution Histone ChIP, and NCAM [J] . Jairo Rodriguez, Jeffrey N. McKnight, Toshio Tsukiyama Current Protocols in Molecular Biology . 2014,第Suppla108期

机译：酵母中核小体位置，占有率和可及性的全基因组分析：核小体定位，高分辨率组蛋白芯片和NCAM

3. Transcription-coupled recruitment of human CHD1 and CHD2 influences chromatin accessibility and histone H3 and H3.3 occupancy at active chromatin regions [J] . Lee Siggens, Lina Cordeddu, Michelle R?nnerblad, Epigenetics & Chromatin . 2015,第1期

机译：人类CHD1和CHD2的转录偶联募集会影响染色质的可及性以及活性染色质区域中组蛋白H3和H3.3的占有率

4. Reveal the Cognitive Process of Deep Learning during Identifying Nucleosome Occupancy and Histone Modification [C] . Jiangyun Li, Jie Zhang, Lei Zuo, Chinese Automation Congress . 2018

机译：在识别核小体占有率和组蛋白修饰时揭示深度学习的认知过程

5. Determinants of Unique DNA Methylation, Histone Modification, and Nucleosome Occupancy at CpG Islands. [D] . Langerman, Justin Bryon. 2014

机译：CpG群岛独特的DNA甲基化，组蛋白修饰和核小体占用的决定因素。

6. Identification of Mutant Versions of the Spt16 Histone Chaperone That Are Defective for Transcription-Coupled Nucleosome Occupancy in Saccharomyces cerevisiae [O] . Sarah J. Hainer, Brittany A. Charsar, Shayna B. Cohen, 2012

机译：突变体版本的Spt16组蛋白伴侣的酿酒酵母的转录耦合核糖体占用的缺陷的鉴定。

7. Identification of Mutant Versions of the Spt16 Histone Chaperone That Are Defective for Transcription-Coupled Nucleosome Occupancy in Saccharomyces cerevisiae [O] . Hainer, Sarah J., Charsar, Brittany A., Cohen, Shayna B., 2012

机译：突变体版本的Spt16组蛋白伴侣的酿酒酵母的转录耦合核糖体占用的缺陷的鉴定。

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2. 用于检测含组蛋白变体的核小体的方法 [P] . 中国专利： CN108107215A . 2018-06-01

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机译：基于鉴定缺陷型突变体中的必需基因，制备用于诊断或控制微生物感染的试剂，特别是对幽门螺杆菌有用

5. Preparing an agent for diagnosis or control of microbial infection, useful particularly against Helicobacter, based on identification of essential genes in defective mutants [P] . 外国专利： DE19927740A1 . 2000-12-21

机译：基于鉴定缺陷型突变体中的必需基因，制备用于诊断或控制微生物感染的试剂，特别是对幽门螺杆菌有用

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Identification of Histone Mutants That Are Defective for Transcription-Coupled Nucleosome Occupancy

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