Reorganization of postmitotic neuronal chromatin accessibility for maturation of serotonergic identity

Abstract
Data availability
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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

The following data sets were generated

(2022) Reorganization of postmitotic neuronal chromatin accessibility for maturation of serotonergic identity
NCBI Gene Expression Omnibus, GSE185737.

http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE185737

The following previously published data sets were used

(2019) Lmx1b is required at multiple stages to build expansive serotonergic axon architectures
NCBI GEO, GSE130514.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE130514
1. Wyler SC
2. Spencer WC
3. Green NH
4. Rood BD
5. Crawford L
6. Craige C
7. Gresch P
8. McMahon DG
9. Beck SG
10. Deneris ES
(2016) Pet-1 Switches Transcriptional Targets Postnatally to Regulate Maturation of Serotonin Neuron Excitability
NCBI GEO, GSE74315.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE74315

Article and author information

Author details

Xinrui L Zhang

Department of Neurosciences, Case Western Reserve University, Cleveland, United States

Competing interests
The authors declare that no competing interests exist.
William C Spencer

Department of Neurosciences, Case Western Reserve University, Cleveland, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9700-8011
Nobuko Tabuchi

Department of Neurosciences, Case Western Reserve University, Cleveland, United States

Competing interests
The authors declare that no competing interests exist.
Meagan M Kitt

Department of Neurosciences, Case Western Reserve University, Cleveland, United States

Competing interests
The authors declare that no competing interests exist.
Evan S Deneris

Department of Neurosciences, Case Western Reserve University, Cleveland, United States

For correspondence
esd@case.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-4211-9934

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.

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).

Copyright

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.