The Role of Retroelements in Centromere Function

逆转录元件在着丝粒功能中的作用

• 批准号: 10652805
• 负责人: Rachel O'Neill
• 金额: $ 7.5万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-19 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10652805
• 关键词: 3-Dimensional; Age; Artificial Human Chromosomes; Bioinformatics; Biological Assay; Cell division; Centromere; Chromatin Modeling; Chromosomal Stability; Chromosome Segregation; Chromosomes; Complex; DNA Transposable Elements; Defect; Elements; Epigenetic Process; Genes; Genetic Materials; Genetic Transcription; Genome; Human; Human Characteristics; Human Chromosomes; Human Genome; Human Pathology; Infertility; Knowledge; Malignant Neoplasms; Meiosis; Mitotic; RNA; Research Personnel; Retroelements; Role; Site; Structure; Techniques; Technology; Testing; Transcript; Transcription Initiation; Work; constriction; daughter cell; fitness; genome integrity; human disease; novel; segregation; telomere

Project Summary With the completion of the Human Genome via the Telomere-to-Telomere Consortium, a complete characterization of the centromeric, pericentromeric, and telomeric regions of every chromosome, including the repeats (satellite remnants, transposable elements (TEs), retroviral insertions, etc.) is conceivable. Although it is widely accepted that centromeres are essential and necessary for proper chromosome segregation during cell division, there is a significant lack in fully understanding centromere dynamics. The limitations of previous technology are at the core of this knowledge gap in centromere entology. Current advances in sequencing and bioinformatic techniques provide an effective means to characterize and identify heterochromatic regions of the genome. Previous studies uncovered centromeric regions as more than long tandem arrays of higher order satellite repeats (HORs) that are comprised of transcriptionally active retroelement insertions displaying that repeat and retroelement transcription is necessary to identify topologically associating domains (TADs), understand the influences on 3D genome structure, and the modulation of activity of genes. We propose to determine how centromere transposable element (cenTEs) sequences influence centromeric function, and thus genome integrity in humans. This project provides a comprehensive analysis of the centromere landscape by studying three objectives. One, determine whether cenTEs are required transcription initiators in centromere assembly by delineating sites of transcription, and testing the impact of transcription initiation on assembly. Two, explain whether cenTEs are epigenetic drivers of centromere chromatin assembly by determining post-transcriptional localization of cenTE RNAs, test the impact of transcripts on centromere assembly, and describe cenTE mobile activity. And three, this study explains whether cenTEs are required for pre-and post- centromere stabilization by utilizing human artificial chromosome assays and long read sequencing. These findings will provide a novel understanding of centromere function and fitness. A comprehensive study such as this is paramount to understanding the complexities of human diseases such as cancer. This current technological golden age enables researchers to ask new questions to old problems utilizing creative techniques.

项目摘要 随着人类基因组通过端粒到端粒联盟的完成， 完整表征的着丝粒，近着丝粒，和端粒区域的每一个 染色体，包括重复序列（卫星残基，转座因子（TE），逆转录病毒 插入等）是可以想象的。尽管人们普遍认为着丝粒是必不可少的， 在细胞分裂过程中，染色体分离是必要的， 完全理解着丝粒动力学。以前技术的局限性是核心 着丝粒昆虫学的知识缺口。目前测序和 生物信息学技术提供了表征和鉴定异染色质的有效手段 基因组的区域。以前的研究发现，着丝粒区域比长 高阶卫星重复序列（HORs）的串联阵列，其由转录上 显示重复序列的活性反转录元件插入和反转录元件转录是必需的 识别拓扑关联结构域（TADs），了解其对3D基因组的影响 结构和基因活性的调节。我们建议确定着丝粒如何 转座因子（cenTE）序列影响着丝粒功能，从而影响基因组 人类的正直这个项目提供了一个全面的分析着丝粒景观 通过研究三个目标。第一，确定cenTE是否需要转录 启动子在着丝粒装配划定的转录位点，并测试的影响， 转录起始于组装。第二，解释centE是否是表观遗传驱动因素， 通过确定cenTE RNA的转录后定位进行着丝粒染色质组装， 测试转录本对着丝粒组装的影响，并描述centTE移动的活性。和 第三，本研究解释了着丝粒前后的稳定是否需要centE 通过利用人类人工染色体测定和长读序测序。这些发现将 提供了一个新的理解着丝粒的功能和健身。一项全面的研究， 因为这对于理解诸如癌症的人类疾病的复杂性至关重要。这 当前的技术黄金时代使研究人员能够对老问题提出新问题 利用创造性的技术。

项目成果

The Earth BioGenome Project 2020: Starting the clock.

• DOI: 10.1073/pnas.2115635118
• 发表时间: 2022-01-25
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Lewin HA;Richards S;Lieberman Aiden E;Allende ML;Archibald JM;Bálint M;Barker KB;Baumgartner B;Belov K;Bertorelle G;Blaxter ML;Cai J;Caperello ND;Carlson K;Castilla-Rubio JC;Chaw SM;Chen L;Childers AK;Coddington JA;Conde DA;Corominas M;Crandall KA;Crawford AJ;DiPalma F;Durbin R;Ebenezer TE;Edwards SV;Fedrigo O;Flicek P;Formenti G;Gibbs RA;Gilbert MTP;Goldstein MM;Graves JM;Greely HT;Grigoriev IV;Hackett KJ;Hall N;Haussler D;Helgen KM;Hogg CJ;Isobe S;Jakobsen KS;Janke A;Jarvis ED;Johnson WE;Jones SJM;Karlsson EK;Kersey PJ;Kim JH;Kress WJ;Kuraku S;Lawniczak MKN;Leebens-Mack JH;Li X;Lindblad-Toh K;Liu X;Lopez JV;Marques-Bonet T;Mazard S;Mazet JAK;Mazzoni CJ;Myers EW;O'Neill RJ;Paez S;Park H;Robinson GE;Roquet C;Ryder OA;Sabir JSM;Shaffer HB;Shank TM;Sherkow JS;Soltis PS;Tang B;Tedersoo L;Uliano-Silva M;Wang K;Wei X;Wetzer R;Wilson JL;Xu X;Yang H;Yoder AD;Zhang G
• 通讯作者: Zhang G

Mechanisms of Rapid Karyotype Evolution in Mammals.

• DOI: 10.3390/genes15010062
• 发表时间: 2023-12-31
• 期刊: Genes
• 影响因子: 3.5