Three-dimensional Chromatin Mapping of Sensory Neurons Reveals That Cohesin-dependent Genomic Domains Are Required for Axonal Regeneration

Overview

Journal bioRxiv

Date 2024 Jun 19

PMID 38895406

Authors

Ilaria Palmisano

Tong Liu

Wei Gao

Luming Zhou

Matthias Merkenschlager

Franziska Muller

Jessica Chadwick

Rebecca Toscano Rivolta

Guiping Kong

James Wd King

Ediem Al-Jibury

Yuyang Yan

Alessandro Carlino

Bryce Collison

Eleonora De Vitis

Sree Gongala

Francesco De Virgiliis

Zheng Wang

Simone Di Giovanni

Affiliations

Soon will be listed here.

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 programme at homeostasis and after sciatic nerve injury in wild-type and cohesin-deficient mouse sensory dorsal root ganglia neurons via combinatorial Hi-C and RNA-seq. We find that cohesin is required for the full induction of the regenerative transcriptional program, by organising 3D genomic domains required for the activation of regenerative genes. Importantly, loss of cohesin results in disruption of chromatin architecture at regenerative genes and severely impaired nerve regeneration. Together, these data provide an original three-dimensional chromatin map of adult sensory neurons in vivo and demonstrate a role for cohesin-dependent chromatin interactions in neuronal regeneration.

References

Cho Y, Sloutsky R, Naegle K, Cavalli V . Injury-induced HDAC5 nuclear export is essential for axon regeneration. Cell. 2013; 155(4):894-908. PMC: 3987749. DOI: 10.1016/j.cell.2013.10.004. View

Rao S, Huang S, St Hilaire B, Engreitz J, Perez E, Kieffer-Kwon K . Cohesin Loss Eliminates All Loop Domains. Cell. 2017; 171(2):305-320.e24. PMC: 5846482. DOI: 10.1016/j.cell.2017.09.026. View

Beagrie R, Pombo A . Gene activation by metazoan enhancers: Diverse mechanisms stimulate distinct steps of transcription. Bioessays. 2016; 38(9):881-93. DOI: 10.1002/bies.201600032. View

Merkenschlager M, Nora E . CTCF and Cohesin in Genome Folding and Transcriptional Gene Regulation. Annu Rev Genomics Hum Genet. 2016; 17:17-43. DOI: 10.1146/annurev-genom-083115-022339. View

Chandran V, Coppola G, Nawabi H, Omura T, Versano R, Huebner E . A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program. Neuron. 2016; 89(5):956-70. PMC: 4790095. DOI: 10.1016/j.neuron.2016.01.034. View

De Virgiliis F, Mueller F, Palmisano I, Chadwick J, Luengo-Gutierrez L, Giarrizzo A . The circadian clock time tunes axonal regeneration. Cell Metab. 2023; 35(12):2153-2164.e4. DOI: 10.1016/j.cmet.2023.10.012. View

Loh Y, Koemeter-Cox A, Finelli M, Shen L, Friedel R, Zou H . Comprehensive mapping of 5-hydroxymethylcytosine epigenetic dynamics in axon regeneration. Epigenetics. 2016; 12(2):77-92. PMC: 5330438. DOI: 10.1080/15592294.2016.1264560. View

Avraham O, Le J, Leahy K, Li T, Zhao G, Cavalli V . Analysis of neuronal injury transcriptional response identifies CTCF and YY1 as co-operating factors regulating axon regeneration. Front Mol Neurosci. 2022; 15:967472. PMC: 9446241. DOI: 10.3389/fnmol.2022.967472. View

Nora E, Goloborodko A, Valton A, Gibcus J, Uebersohn A, Abdennur N . Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization. Cell. 2017; 169(5):930-944.e22. PMC: 5538188. DOI: 10.1016/j.cell.2017.05.004. View

10.

Luo X, Liu Y, Dang D, Hu T, Hou Y, Meng X . 3D Genome of macaque fetal brain reveals evolutionary innovations during primate corticogenesis. Cell. 2021; 184(3):723-740.e21. DOI: 10.1016/j.cell.2021.01.001. View

11.

Tedeschi A, Dupraz S, Laskowski C, Xue J, Ulas T, Beyer M . The Calcium Channel Subunit Alpha2delta2 Suppresses Axon Regeneration in the Adult CNS. Neuron. 2016; 92(2):419-434. DOI: 10.1016/j.neuron.2016.09.026. View

12.

Lindner R, Puttagunta R, Nguyen T, Di Giovanni S . DNA methylation temporal profiling following peripheral versus central nervous system axotomy. Sci Data. 2015; 1:140038. PMC: 4411011. DOI: 10.1038/sdata.2014.38. View

13.

Ma T, Willis D . What makes a RAG regeneration associated?. Front Mol Neurosci. 2015; 8:43. PMC: 4528284. DOI: 10.3389/fnmol.2015.00043. View

14.

Sams D, Nardone S, Getselter D, Raz D, Tal M, Rayi P . Neuronal CTCF Is Necessary for Basal and Experience-Dependent Gene Regulation, Memory Formation, and Genomic Structure of BDNF and Arc. Cell Rep. 2016; 17(9):2418-2430. DOI: 10.1016/j.celrep.2016.11.004. View

15.

Hansen A, Cattoglio C, Darzacq X, Tjian R . Recent evidence that TADs and chromatin loops are dynamic structures. Nucleus. 2017; 9(1):20-32. PMC: 5990973. DOI: 10.1080/19491034.2017.1389365. View

16.

Finelli M, Wong J, Zou H . Epigenetic regulation of sensory axon regeneration after spinal cord injury. J Neurosci. 2013; 33(50):19664-76. PMC: 3858634. DOI: 10.1523/JNEUROSCI.0589-13.2013. View

17.

Fujita Y, Masuda K, Bando M, Nakato R, Katou Y, Tanaka T . Decreased cohesin in the brain leads to defective synapse development and anxiety-related behavior. J Exp Med. 2017; 214(5):1431-1452. PMC: 5413336. DOI: 10.1084/jem.20161517. View

18.

Rao S, Huntley M, Durand N, Stamenova E, Bochkov I, Robinson J . A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell. 2014; 159(7):1665-80. PMC: 5635824. DOI: 10.1016/j.cell.2014.11.021. View

19.

Cuadrado A, Remeseiro S, Grana O, Pisano D, Losada A . The contribution of cohesin-SA1 to gene expression and chromatin architecture in two murine tissues. Nucleic Acids Res. 2015; 43(6):3056-67. PMC: 4381060. DOI: 10.1093/nar/gkv144. View

20.

Lau J, Minett M, Zhao J, Dennehy U, Wang F, Wood J . Temporal control of gene deletion in sensory ganglia using a tamoxifen-inducible Advillin-Cre-ERT2 recombinase mouse. Mol Pain. 2011; 7:100. PMC: 3260248. DOI: 10.1186/1744-8069-7-100. View