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

> **NIH NIH F30** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $51,036

## Abstract

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.

## Key facts

- **NIH application ID:** 10161609
- **Project number:** 5F30MH122173-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Xinrui Zhang
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $51,036
- **Award type:** 5
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10161609

## Citation

> US National Institutes of Health, RePORTER application 10161609, Regulation of Pet1/FEV binding and chromatin accessibility during serotonergic neuron development (5F30MH122173-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10161609. Licensed CC0.

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