Regulation of Pet1/FEV binding and chromatin accessibility during serotonergic neuron development

血清素能神经元发育过程中 Pet1/FEV 结合和染色质可及性的调节

基本信息

  • 批准号:
    10161609
  • 负责人:
  • 金额:
    $ 5.1万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-01-01 至 2023-12-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT The neurotransmitter serotonin (5-HT) is implicated in the pathophysiology of many psychiatric and neurodevelopmental disorders, including anxiety, depression, autism, schizophrenia, attention- deficit/hyperactivity disorder, and compulsive disorders. How serotonin neurons mature and acquire their transmitter identity and adult characteristics remain poorly understood. During the embryonic and early postnatal period, lineage specific gene expression patterns of serotonin neurons are orchestrated by a network of developmentally critical transcription factors, including the ETS family transcription factor Pet1 (human ortholog FEV) that is essential for the establishment of serotonin neurotransmission. Intriguingly, we recently found Pet1 switches targets during fetal to early postnatal transition, from controlling the upregulation of 5-HT synthesis genes during fetal life to activating gene required for synaptic excitability during the postnatal period. This study investigates the hypothesis that the changes in the chromatin accessibility of cis-regulatory elements dictate the repertoire of transcriptional targets that are available for Pet1 regulation during development. Furthermore, I hypothesize that Pet1 binding also shapes chromatin architecture to direct the gene expression trajectories of developing serotonin neurons. To test these hypotheses, in Aim 1, I will map the global open chromatin landscape of serotonin neurons using Assay for Transposase Accessible Chromatin with high throughput sequencing (ATAC-seq) at multiple embryonic and early postnatal developmental time points, and investigate the relation of open chromatin to 5-HT neuron gene expression. In Aim 2, I will analyze the changes in Pet1 DNA occupancy during the same stages of serotonin neuron development as in Aim 1 using Pet1 chromatin immunoprecipitation coupled to high throughput sequencing (ChIP-seq), and determine the importance of Pet1 for developmentally critical chromatin remodeling or maintenance by performing ATAC- seq in Pet1 knockout mice. By elucidating how Pet1 dynamically regulates gene expression critical for the maturation of serotonin neurons, I will provide insight into the pathophysiology of the neuropsychiatric conditions in which serotonin gene expression is thought to be perturbed. Additionally, this study provides valuable training opportunity for me to gain technical proficiency in mouse genetics and transcriptomic and epigenetic profiling, broad conceptual knowledge in molecular neuroscience, and experience with experimental design, data interpretation, and oral and written communication that are crucial for my own growth as a physician-scientist in training.
项目总结/文摘

项目成果

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Xinrui Zhang其他文献

Xinrui Zhang的其他文献

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{{ truncateString('Xinrui Zhang', 18)}}的其他基金

Regulation of Pet1/FEV binding and chromatin accessibility during serotonergic neuron development
血清素能神经元发育过程中 Pet1/FEV 结合和染色质可及性的调节
  • 批准号:
    10542353
  • 财政年份:
    2020
  • 资助金额:
    $ 5.1万
  • 项目类别:
Regulation of Pet1/FEV binding and chromatin accessibility during serotonergic neuron development
血清素能神经元发育过程中 Pet1/FEV 结合和染色质可及性的调节
  • 批准号:
    9911041
  • 财政年份:
    2020
  • 资助金额:
    $ 5.1万
  • 项目类别:
Regulation of Pet1/FEV binding and chromatin accessibility during serotonergic neuron development
血清素能神经元发育过程中 Pet1/FEV 结合和染色质可及性的调节
  • 批准号:
    10320980
  • 财政年份:
    2020
  • 资助金额:
    $ 5.1万
  • 项目类别:

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