The role of DOT1L methyltransferase in controlling the noncoding transcriptome
DOT1L 甲基转移酶在控制非编码转录组中的作用
基本信息
- 批准号:10809451
- 负责人:
- 金额:$ 0.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-05-22 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:AnimalsAntibodiesAntisense RNAAntiviral ResponseBindingBinding ProteinsBioethicsCaenorhabditis elegansCell NucleusCellsChromatinClustered Regularly Interspaced Short Palindromic RepeatsCodeComplementary RNAComplexCongenital AbnormalityCytoplasmDataDevelopmentDevelopmental GeneDouble-Stranded RNAEnhancersEnzymesExperimental GeneticsFishesFutureGene ExpressionGene Expression RegulationGene SilencingGenerationsGenesGeneticGenetic TranscriptionGenomic approachGenomicsGoalsHigh School StudentHistone H2AHistone H3Homologous GeneHumanImmunoprecipitationLaboratoriesLinkLysineMalignant NeoplasmsMammalian CellMammalsMediatorMessenger RNAMethylationMethyltransferaseMicroRNAsModelingMolecularMutationNamesNematodaNuclear RNANucleotidesPHD FingerPathogenesisPathway interactionsPhenotypePlantsProcessProductionProteinsPublishingRNARNA BindingRNA InterferenceRNA-Protein InteractionResearchRoleSmall Interfering RNASmall RNASystemTestingTitrationsTranscriptional ActivationTranscriptional RegulationTransgenesUntranslated RNAVariantViralVirusWorkYeastsZebrafishZinc Fingersbasedeep sequencinggenetic approachgenome wide methylationglobal run on sequencinghuman diseaseinsightinterestleukemialoss of functionmRNA Precursormalignant breast neoplasmmutantnovelpromoterprotein complexrecruittranscriptomeundergraduate student
项目摘要
The broad goal of our research is to understand how gene expression is regulated during animal development.
Our specific interest is in finding natural regulators of endogenous double-stranded RNA production and nuclear
RNA interference. In this regard, we are focusing on the relationship between RNA interference and the histone
H3 lysine 79 DOT1L methyltransferase complex. A connection between the DOT1L interacting partner ZFP-1
(AF10 in mammals) and RNAi in C. elegans was suggested by genetic experiments 13-15 years ago. To
understand this connection, my laboratory undertook molecular and genomic studies of ZFP-1 and DOT1L.
These studies not only confirmed the connection to RNAi, but also provided novel insights about the conserved
role of DOT1L in transcription regulation. The DOT1L enzyme is essential for mammalian development and has
been implicated in the pathogenesis of leukemia and breast cancer. However, the exact role of DOT1L in gene
regulation is not clear. Preliminary work from our lab has begun to reveal this role; we have discovered that
DOT1L and H3K79 methylation globally suppress non-coding RNA transcription in C. elegans, including that of
antisense and enhancer RNAs. Our preliminary data strongly suggest ectopic dsRNA formation and small RNA
production upon DOT1L loss-of-function. Our main goals are: 1) to detect and characterize these dsRNA and
small RNA molecules in C. elegans; 2) to explore the possibility that the dsRNA suppressing function of DOT1L
is conserved in mammals, and 3) to investigate the mechanism of transcription regulation by DOT1L in
development using the C. elegans and zebrafish systems.
The project is not specific to bioethics research or capacity building in bioethics. Undergraduate and high school
students will actively participate in the proposed research.
我们研究的主要目标是了解在动物发育过程中基因表达是如何被调控的。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Small RNAs Worm Up Transgenerational Epigenetics Research.
- DOI:10.3390/dna1020005
- 发表时间:2021-12
- 期刊:
- 影响因子:0
- 作者:Grishok A
- 通讯作者:Grishok A
DOT1L stimulates MYC/Mondo transcription factor activity by promoting its degradation cycle on chromatin.
DOT1L 通过促进染色质上的降解循环来刺激 MYC/Mondo 转录因子活性。
- DOI:10.1101/2024.02.06.579191
- 发表时间:2024
- 期刊:
- 影响因子:0
- 作者:Sepulveda,GianP;Gushchanskaia,EkaterinaS;Mora-Martin,Alexandra;Esse,Ruben;Nikorich,Iana;Ceballos,Ainhoa;Kwan,Julian;Blum,BenjaminC;Dholiya,Prakruti;Emili,Andrew;Perissi,Valentina;Cardamone,MariaD;Grishok,Alla
- 通讯作者:Grishok,Alla
Shaking up the silence: consequences of HMGN1 antagonizing PRC2 in the Down syndrome brain.
- DOI:10.1186/s13072-022-00471-6
- 发表时间:2022-12-03
- 期刊:
- 影响因子:3.9
- 作者:
- 通讯作者:
The proline-rich domain of MML-1 is biologically important but not required for localization to target promoters.
- DOI:10.17912/micropub.biology.000498
- 发表时间:2021
- 期刊:
- 影响因子:0
- 作者:Ceballos A;Esse R;Grishok A
- 通讯作者:Grishok A
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Alla Grishok其他文献
Alla Grishok的其他文献
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{{ truncateString('Alla Grishok', 18)}}的其他基金
The role of DOT1L methyltransferase in controlling the noncoding transcriptome
DOT1L 甲基转移酶在控制非编码转录组中的作用
- 批准号:
10581918 - 财政年份:2020
- 资助金额:
$ 0.58万 - 项目类别:
The role of DOT1L methyltransferase in controlling the noncoding transcriptome
DOT1L 甲基转移酶在控制非编码转录组中的作用
- 批准号:
10460485 - 财政年份:2020
- 资助金额:
$ 0.58万 - 项目类别:
The role of DOT1L methyltransferase in controlling the noncoding transcriptome
DOT1L 甲基转移酶在控制非编码转录组中的作用
- 批准号:
10223379 - 财政年份:2020
- 资助金额:
$ 0.58万 - 项目类别:
The role of DOT1L methyltransferase in controlling the noncoding transcriptome
DOT1L 甲基转移酶在控制非编码转录组中的作用
- 批准号:
10669669 - 财政年份:2020
- 资助金额:
$ 0.58万 - 项目类别:
Regulation of RNA processing and transcription by endogenous RNAi
内源性 RNAi 对 RNA 加工和转录的调节
- 批准号:
8757055 - 财政年份:2014
- 资助金额:
$ 0.58万 - 项目类别:
Regulation of RNA processing and transcription by endogenous RNAi
内源性 RNAi 对 RNA 加工和转录的调节
- 批准号:
9010960 - 财政年份:2014
- 资助金额:
$ 0.58万 - 项目类别:
Investigating the Potential of Endogenous RNAi in Mediating Adaptation to Environ
研究内源性 RNAi 介导环境适应的潜力
- 批准号:
7840683 - 财政年份:2009
- 资助金额:
$ 0.58万 - 项目类别:
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