Epigenetic regulation through the formation and resolution of R loops
通过 R 环的形成和解析进行表观遗传调控
基本信息
- 批准号:9350668
- 负责人:
- 金额:$ 285万
- 依托单位:
- 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:2017-09-30 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAmyotrophic Lateral SclerosisAttentionCell NucleusChromatinChromatin StructureComplexDNADNA PackagingDNA SequenceDevelopmentDimensionsDiseaseDistantEpigenetic ProcessFragile X SyndromeFriedreich AtaxiaGene Expression RegulationGenesGenetic TranscriptionGenomeGenomic SegmentHybridsInvadedLeadMalignant NeoplasmsMessenger RNAMethodologyMolecularMutationNerve DegenerationNeurodegenerative DisordersPathogenicityPathologyPost-Translational Protein ProcessingProcessRNAResolutionRoleUntranslated RNAchromatin modificationds-DNAepigenetic regulationnervous system disordernovel therapeuticsnucleic acid structurerepairedscreeningtherapeutic candidatetool
项目摘要
Project Summary
Chromatin, the packaging for DNA in the eukaryotic nucleus, is a dynamic entity that is affected
by cellular processes such as replication, transcription and repair. Our views on gene regulation
have evolved from simple notions about changes in DNA sequence, to a more complex
perspective that takes into account multiple epigenetic factors such as chromatin structure,
chromatin composition and three-dimensional genome organization. Over the last decade, much
attention has been devoted to epigenetic alterations in chromatin, including post translational
modifications of chromatin components, long non-coding RNAs that localize to and regulate
genes, and most recently large scale changes in genome organization that affect interactions
between distant genomic regions. However, one aspect of epigenetic gene regulation that has
received a surprisingly small amount of attention is the changes in chromatin structure that occur
as a consequence of transcription. Transcription is pervasive, with over 90% of the eukaryotic
genome producing RNAs. The common chromatin structures that result from, and depend on
transcription, such as R loops, are likely to contribute significantly to epigenetic gene regulation.
But exactly how is not known. R loops are triplex nucleic acid structures formed during
transcription when an RNA, either an mRNA or a long non-coding RNA, invades dsDNA, forming
an RNA-DNA hybrid and a displaced ssDNA. Under normal conditions, R loops function in all
aspects of gene regulation, but aberrant formation of R loops, or mutations in components that
regulate them, is associated with several neurodegenerative diseases and cancers. R loops are
especially relevant in repeat expansion disorders where their unscheduled formation results in
aberrant transcription and disease pathology. But what causes R loops to form aberrantly or be
resolved once created remains unknown. Identifying the molecular players that function at R
loops is an important step toward targeting R loops for therapies for neurological disorders. We
will develop new methodologies to isolate and identify R loop regulators, create a framework of
molecular tools to elucidate mechanisms of these regulators and finally undertake a molecular
screening approach to identify factors that facilitate transcription through a pathogenic R loop
forming repeat. As a result, we expect to identify new regulators of R loops that can lead to novel
therapeutic candidates for neurodegenerative repeat expansion disorders.
项目总结
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Targeted Nuclease Approaches for Mapping Native R-Loops.
用于绘制天然 R 环的靶向核酸酶方法。
- DOI:10.1007/978-1-0716-2477-7_25
- 发表时间:2022
- 期刊:
- 影响因子:0
- 作者:Wulfridge,Phillip;Yan,Qingqing;Sarma,Kavitha
- 通讯作者:Sarma,Kavitha
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{{ truncateString('Kavitha Sarma', 18)}}的其他基金
ADNP mechanisms in R-loop regulation during differentiation
ADNP 在分化过程中 R 环调节的机制
- 批准号:
10444141 - 财政年份:2022
- 资助金额:
$ 285万 - 项目类别:
Developing a genomic toolkit to identify RNAs within non-canonical DNA structures
开发基因组工具包来识别非规范 DNA 结构中的 RNA
- 批准号:
10708851 - 财政年份:2022
- 资助金额:
$ 285万 - 项目类别:
Developing a genomic toolkit to identify RNAs within non-canonical DNA structures
开发基因组工具包来识别非规范 DNA 结构中的 RNA
- 批准号:
10506451 - 财政年份:2022
- 资助金额:
$ 285万 - 项目类别:
CTCF-dependent mechanisms of ATRX in neuronal differentiation
ATRX 在神经元分化中的 CTCF 依赖性机制
- 批准号:
10625522 - 财政年份:2022
- 资助金额:
$ 285万 - 项目类别:
Molecular and neurodevelopmental consequences of ADNP mutation
ADNP 突变的分子和神经发育后果
- 批准号:
10372679 - 财政年份:2021
- 资助金额:
$ 285万 - 项目类别:
Molecular and neurodevelopmental consequences of ADNP mutation
ADNP 突变的分子和神经发育后果
- 批准号:
10491348 - 财政年份:2021
- 资助金额:
$ 285万 - 项目类别:
Deciphering the Role of MacroH2A in Non-coding RNA Mediated Silencing
解读 MacroH2A 在非编码 RNA 介导的沉默中的作用
- 批准号:
8044167 - 财政年份:2010
- 资助金额:
$ 285万 - 项目类别:
Deciphering the Role of MacroH2A in Non-coding RNA Mediated Silencing
解读 MacroH2A 在非编码 RNA 介导的沉默中的作用
- 批准号:
7806710 - 财政年份:2010
- 资助金额:
$ 285万 - 项目类别:
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