Enhancer RNAs Boost MYC-Chromatin Interaction to Regulate Gene Expression and Tumorigenesis
Enhancer RNAs Boost MYC-Chromatin Interaction to Regulate Gene Expression and Tumorigenesis
批准号:
10716358
负责人:
Da Yang
金额:
$43.4万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-09-01 至 2028-08-31
关键词:
BindingBiological AssayBromodomains and extra-terminal domain inhibitorChIP-seqChromatinChromatin Interaction Analysis by Paired-End Tag SequencingClustered Regularly Interspaced Short Palindromic RepeatsCommunitiesDNADNA BindingDataDimensionsDimerizationEMSAEnhancersEstrogen Receptor alphaEstrogen receptor positiveFoundationsGREB1 geneGene AmplificationGene ExpressionGene Expression RegulationGoalsGrowthIn VitroInvadedInvestigationMYC Family ProteinMalignant NeoplasmsMammary Gland ParenchymaMediatingMolecularOncogenesOncogenicPathologicPhysiologicalPlayRNARNA BindingRNA-Binding ProteinsRegulationRegulator GenesReporterResearchRoleSmall Interfering RNATechnologyTestingTranscriptional Regulationdesignin vivoknock-downmalignant breast neoplasmnovelnovel strategiesoverexpressionpreferencepromoterrecruittooltranscription factortumortumor growthtumorigenesis
中文摘要
增强子rna促进myc -染色质相互作用调节基因表达和肿瘤发生
英文摘要
Enhancer RNAs Boost MYC-Chromatin Interaction to Regulate Gene Expression and Tumorigenesis
Summary: Our long-term goal is to determine how MYC’s RNA binding function contributes to its role as a
master regulator of gene expression in physiological and pathological conditions. In last three decades, MYC
has been extensively studied as a DNA-binding transcription factor. However, whether MYC can interact with
RNA and, if yes, how such interactions would contribute to MYC function are poorly understood.
In our preliminary study, we have shown that MYC may be a novel RNA-binding protein with a
preference to bind with enhancer RNAs (eRNAs). In addition to characterizing MYC as an RNA-binding
protein, we have also identified a MYC-bound eRNA MERG1 that can regulate breast cancer growth via
recruiting MYC to its cognate enhancer. With these observations, we hypothesize that (1) MYC is an RNA-
binding protein and (2) eRNA-mediated MYC-chromatin binding is important for MYC’s transcriptional
regulation and oncogenic function. We propose three specific aims to test our hypotheses. In Aim 1, we will
investigate if MERG1 is an oncogenic eRNA in ER+ breast cancer. In aim 2, we will investigate the molecular
mechanism of MYC’s RNA binding function. In aim 3, we will build MYC-eRNA regulatory network.
Our project will add a new dimension to mechanistically study the MYC-mediated gene regulation.
Successful completion of the project will establish novel tools to investigate MYC-RNA binding function for
the broader MYC research community. The investigation of MYC RNA binding function will also lay the
foundation to develop novel strategy to target MYC in cancer.
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