Reorganization of postmitotic neuronal chromatin accessibility for maturation of serotonergic identity
- Case Western Reserve University, United States
Abstract
Assembly of transcriptomes encoding unique neuronal identities requires selective accessibility of transcription factors to cis-regulatory sequences in nucleosome-embedded postmitotic chromatin. Yet, the mechanisms controlling postmitotic neuronal chromatin accessibility are poorly understood. Here, we show that unique distal enhancers define the Pet1 neuron lineage that generates serotonin (5-HT) neurons in mice. Heterogeneous single cell chromatin landscapes are established early in postmitotic Pet1 neurons and reveal the putative regulatory programs driving Pet1 neuron subtype identities. Distal enhancer accessibility is highly dynamic as Pet1 neurons mature, suggesting the existence of regulatory factors that reorganize postmitotic neuronal chromatin. We find that Pet1 and Lmx1b control chromatin accessibility to select Pet1-lineage specific enhancers for 5-HT neurotransmission. Additionally, these factors are required to maintain chromatin accessibility during early maturation suggesting that postmitotic neuronal open chromatin is unstable and requires continuous regulatory input. Together our findings reveal postmitotic transcription factors that reorganize accessible chromatin for neuron specialization.
Data availability
Sequencing data have been deposited in GEO under accession code GSE185737
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Reorganization of postmitotic neuronal chromatin accessibility for maturation of serotonergic identityNCBI Gene Expression Omnibus, GSE185737.
Article and author information
Author details
Funding
National Institute of Mental Health (RO1 MH117643)
- Evan S Deneris
National Institute of Mental Health (RO1 MH062723)
- Evan S Deneris
National Institute of Mental Health (F30 MH122173)
- Xinrui L Zhang
National Institute of General Medical Sciences (T32 GM007250)
- Xinrui L Zhang
Uehara Memorial Foundation (201940009)
- Nobuko Tabuchi
Japan Society for the Promotion of Science (Overseas Research Fellowship)
- Nobuko Tabuchi
National Institute of General Medical Sciences (T32 GM008056)
- Meagan M Kitt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Paschalis Kratsios, University of Chicago, United States
Ethics
Animal experimentation: Animal experimentation: All animal procedures used in this study were in strict accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Case Western Reserve University School of Medicine Institutional Animal Care and Use Committee (Animal Welfare Assurance Number A3145-01, protocol #: 2014-0044).
Version history
- Preprint posted: October 14, 2021 (view preprint)
- Received: November 29, 2021
- Accepted: April 12, 2022
- Accepted Manuscript published: April 26, 2022 (version 1)
- Version of Record published: May 12, 2022 (version 2)
Copyright
© 2022, Zhang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Reorganization of postmitotic neuronal chromatin accessibility for maturation of serotonergic identity
eLife 11:e75970.
https://doi.org/10.7554/eLife.75970
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