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Transcriptome regulation during mitosis

有丝分裂期间的转录组调控

基本信息

批准号：
10359186
负责人：
Michael Demian Blower
金额：
$ 33.99万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
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/10359186
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

项目摘要

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.

项目总结