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The epigenetic mechanism of enhancer RNA in behavioral plasticity

增强子RNA在行为可塑性中的表观遗传机制

基本信息

批准号：
9327079
负责人：
Tae-Kyung Kim
金额：
$ 34.78万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-15 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9327079
关键词：
Adverse effects Alpha Cell Architecture Autistic Disorder Behavior Binding Biochemical Biological Assay Biological Models Brain Cell Nucleus Cells Co-Immunoprecipitations Code Cognitive Complex Development Elongation Factor Enhancers Epigenetic Process Epilepsy Exhibits FOS gene Fluorescent in Situ Hybridization Functional disorder Gene Expression Gene Expression Regulation Gene Targeting Genes Genetic Genetic Transcription Genetic study High-Throughput Nucleotide Sequencing Hippocampus (Brain)Human Human Genetics Immediate-Early Genes Impairment Individual Label Learning Link Long-Term Potentiation Maintenance Mass Spectrum Analysis Memory Messenger RNA Methyl-CpG-Binding Protein 2 Modeling Molecular Mutation Names Nature Neuronal Plasticity Neurons Neurophysiology - biologic function Pathway interactions Phase Play Production Proteins RNA RNA Polymerase II RNA Sequences RNA chemical synthesis Regulation Rett Syndrome Role Rubinstein-Taybi Syndrome Sensory Signal Pathway Signal Transduction Slice Source Stimulus Synapses Synaptic plasticity Testing Translating Untranslated RNA Ursidae Family base behavioral plasticity clinically significant cognitive function conditioned fear crosslinking and immunoprecipitation sequencing experience experimental study genome-wide genome-wide analysis insight interdisciplinary approach knock-down long term memory mRNA Expression mammalian genome memory consolidation memory process negative elongation factor nervous system disorder neural circuit neuroregulation novel overexpression programs promoter public health relevance relating to nervous system response spatiotemporal transcriptome

项目摘要

DESCRIPTION (provided by applicant): A substantial body of evidence suggests that many neurological diseases may commonly result from perturbations of activity-dependent changes in neural functions. During brain development, sensory stimulation-dependent modulation of individual neurons and circuits involves not only structural and functional changes in local synaptic connections, but also a cell-wide arrangement for sustained adaptive responses. Sensory experience-dependent gene expression is an integral mechanism of cell-wide adaptation as it is responsible for the stimulus-specific production and deployment of proteins with various functions in individual neurons, which are required for appropriate adaptive responses. In keeping with this notion, mutations in several genes implicated in the signaling pathways from the synapse to the nucleus have been linked to various neurological diseases such as autism and epilepsy, suggesting that the disruption of activity-dependent gene expression programs under specific circumstances, such as activity-dependent learning can elicit a pathophysiological condition. As such, the study to understand how genetic and epigenetic programs accurately translate sensory information into changes in relevant neural circuits and cognitive behavior bears clinical significance. A recent genome-wide study revealed that a novel class of long non-protein coding RNAs (lncRNAs) called eRNAs (enhancer RNAs) is rapidly expressed from thousands of neuronal enhancers when neurons are excited. The eRNA is quite unique among various types of lncRNAs in that its expression is rapid, transient, and dynamically controlled by sensory stimulation-evoked neuronal activity. The pervasive nature and strong expression correlation with nearby mRNAs suggest a provoking idea that the eRNA might be functionally implicated in the sensory stimulation-induced neural and behavioral plasticity by playing an active role in neural gene expression. Initial analysis of the eRNA function further supports this hypothesis. Given that less than 2% of the mammalian genome accounts for protein-coding genes, an increasing number of mutations associated with neurological diseases will be found to reside in the non-coding regions as human genetic studies continue to advance. The proposed study involves a multidisciplinary approach to examine the role of eRNA in activity-dependent transcription and subsequent changes in synaptic and behavioral plasticity. The eRNA-dependent epigenetic mechanism may represent a new layer of complexity in the molecular architecture of many neurological diseases.

描述（由申请人提供）：

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

SET7/9 methylation of the pluripotency factor LIN28A is a nucleolar localization mechanism that blocks let-7 biogenesis in human ESCs.

多能因子LIN28A的SET7/9甲基化是一种核仁定位机制，可阻止人ESC中的Let-7生物发生。

DOI：
10.1016/j.stem.2014.10.016
发表时间：
2014-12-04
期刊：
CELL STEM CELL
影响因子：
23.9
作者：
Kim, Seung-Kyoon;Lee, Hosuk;Han, Kyumin;Kim, Sang Cheol;Choi, Yoonjung;Park, Sang-Wook;Bak, Geunu;Lee, Younghoon;Choi, Jung Kyoon;Kim, Tae-Kyung;Han, Yong-Mahn;Lee, Daeyoup
通讯作者：
Lee, Daeyoup

Stimulus-specific combinatorial functionality of neuronal c-fos enhancers.