Three-dimensional chromatin mapping of sensory neurons reveals that promoter-enhancer looping is required for axonal regeneration
Author(s)
Type
Journal Article
Abstract
The in vivo three-dimensional genomic architecture of adult mature neurons at homeostasis and after medically relevant perturbations such as axonal injury remains elusive. Here, we address this knowledge gap by mapping the three-dimensional chromatin architecture and gene expression program at homeostasis and after sciatic nerve injury in wild-type and cohesin-deficient mouse sensory dorsal root ganglia neurons via combinatorial Hi-C, promoter-capture Hi-C, CUT&Tag for H3K27ac and RNA-seq. We find that genes involved in axonal regeneration form long-range, complex chromatin loops, and that cohesin is required for the full induction of the regenerative transcriptional program. Importantly, loss of cohesin results in disruption of chromatin architecture and severely impaired nerve regeneration. Complex enhancer-promoter loops are also enriched in the human fetal cortical plate, where the axonal growth potential is highest, and are lost in mature adult neurons. Together, these data provide an original three-dimensional chromatin map of adult sensory neurons in vivo and demonstrate a role for cohesin-dependent long-range promoter interactions in nerve regeneration.
Date Issued
2024-09-17
Date Acceptance
2024-08-10
Citation
Proceedings of the National Academy of Sciences of USA, 2024, 121 (38)
ISSN
0027-8424
Publisher
National Academy of Sciences
Journal / Book Title
Proceedings of the National Academy of Sciences of USA
Volume
121
Issue
38
Copyright Statement
Copyright © 2024 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
This article is a PNAS Direct Submission. R.G. is a guest editor invited by the Editorial Board.
This article is a PNAS Direct Submission. R.G. is a guest editor invited by the Editorial Board.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39254997
Subjects
Animals
Axons
Cell Cycle Proteins
Chromatin
Chromosomal Proteins, Non-Histone
Cohesins
Enhancer Elements, Genetic
Ganglia, Spinal
Humans
Mice
Nerve Regeneration
Promoter Regions, Genetic
Sciatic Nerve
Sensory Receptor Cells
cohesin
nerve regeneration
promoter loops
regeneration program
three-dimensional chromatin architecture
Publication Status
Published
Coverage Spatial
United States
Article Number
e2402518121
Date Publish Online
2024-09-10