Transcriptome regulation during mitosis

有丝分裂期间的转录组调控

• 批准号: 10212833
• 负责人: Michael Demian Blower
• 金额: $ 29.71万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10212833
• 关键词: Affect; Aneuploidy; Binding; Cancer Etiology; Cell Cycle; Cell Nucleus; Cell division; Cells; Centromere; Chromatin; Chromosome Condensation; Chromosome Segregation; Chromosomes; Complex; Congenital Abnormality; Cytoplasm; Development; Down-Regulation; Ensure; Excision; Exhibits; Failure; Gene Expression; Gene Expression Profile; Gene Silencing; Genes; Genetic Transcription; Genomic Segment; Goals; Inherited; Interphase; Kinetochores; Lead; Malignant Neoplasms; Mediating; Meiosis; Messenger RNA; Microtubules; Mitosis; Mitotic; Mitotic Chromosome; Mitotic spindle; Molecular; Monitor; Nuclear; Nuclear Envelope; Nuclear RNA; Pattern; Phosphorylation; Play; Process; Prophase; Proteins; RNA; RNA Binding; RNA analysis; Recycling; Regulation; Role; Signaling Molecule; Sister Chromatid; Site; Spontaneous abortion; Testing; Time; Transcriptional Regulation; Untranslated RNA; Work; cohesin; daughter cell; insight; novel; programs; recruit; transcriptome; tumor progression

Project Summary Accurate chromosome segregation during mitosis and meiosis is critical for viability and development. Errors in chromosome segregation lead to aneuploidy, which is closely correlated with cancer. In order to ensure accurate chromosome segregation duplicated sister chromatids must be dramatically condensed and individualized upon entry into mitosis. Accurate chromosome distribution during mitosis depends on the interaction of duplicated sister chromatids with the microtubules of the mitotic spindle. Each chromosome contains one centromere that serves as the site for the formation of the kinetochore. At nuclear envelope breakdown, proteins important for kinetochore:microtubule (K:MT) attachment and signaling molecules that monitor K:MT attachment are recruited to the kinetochore. Successful completion of cell division requires the coordinated regulation of centromere/kinetochore assembly, kinetochore:microtubule attachment and chromosome condensation. Decades of work have identified hundreds of proteins that regulate various aspects of mitosis. However, very little is known about regulation of the transcriptome during mitosis. Recent work has demonstrated that remodeling of the transcriptome plays an important role in mitotic regulation. This proposal will study two fundamental aspects of transcriptome remodeling during mitosis. First, during mitosis, the majority of nuclear transcription is blocked, however, centromeres escape transcriptional down-regulation. Surprisingly, very little is known about the mechanism of transcriptional inhibition during mitosis or how disruption of mitotic transcriptional inhibition impacts the fidelity of chromosome segregation. It is also unknown if the process of mitotic transcriptional inhibition contributes to changing gene expression patterns. Second, during interphase hundreds to thousands of RNAs are retained in the nucleus where they bind to chromatin and regulate nuclear organization and gene expression. During mitosis many nuclear RNAs are released from chromatin, yet little is known about the mechanism of RNA removal from chromatin during mitosis. Additionally, it is unknown how disruption of RNA release from chromatin impacts the process of chromosome segregation or gene expression following mitosis. Our work will investigate how the transcriptome is remodeled during mitosis and how this contributes to accurate chromosome segregation.

项目摘要 有丝分裂和减数分裂过程中准确的染色体分离对存活率和 发展。染色体分离的错误会导致非整倍体，这是密切相关的 得了癌症。为了确保准确的染色体分离，复制了姐妹染色单体 在进入有丝分裂时必须显著浓缩和个体化。准确 有丝分裂过程中染色体的分布取决于复制姐妹的相互作用 有丝分裂纺锤体的微管的染色单体。每条染色体包含一条染色体 着丝粒，着丝粒是着丝粒形成的场所。在核包膜上 动粒的重要蛋白质：微管(K：MT)连接和信号转导 监控K：MT附着的分子被招募到动粒上。成功 细胞分裂的完成需要着丝粒/着丝粒的协调调控 组装，着丝粒：微管附着和染色体凝聚。 几十年的工作已经确定了数百种蛋白质，它们调控着 有丝分裂。然而，对转录组在有丝分裂过程中的调控知之甚少。 最近的工作表明，转录组的重塑在 有丝分裂调控。这项提案将研究转录组重塑的两个基本方面。 在有丝分裂期间。首先，在有丝分裂期间，大多数核转录被阻止，然而， 着丝粒逃脱转录下调。令人惊讶的是，人们对此知之甚少 有丝分裂过程中转录抑制的机制或有丝分裂转录如何中断 抑制会影响染色体分离的保真度。同样未知的是，这一过程 有丝分裂转录抑制有助于改变基因表达模式。第二, 在间期，成百上千的RNA保留在它们结合的细胞核中 染色质，调节核组织和基因表达。在有丝分裂期间有很多 核RNA是从染色质中释放出来的，但人们对其作用机制知之甚少。 在有丝分裂过程中从染色质中去除。此外，目前尚不清楚RNA是如何被破坏的 染色质的释放影响染色体分离或基因表达的过程 在有丝分裂之后。我们的工作将研究转录组在有丝分裂期间是如何重塑的。 以及这如何有助于准确的染色体分离。