An expansion of the non-coding genome and its regulatory potential underlies vertebrate neuronal diversity
Name
nihms-1754003.pdf
Description
Accepted version
Size
2.21 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Closser, Michael
Guo, Yuchun
Wang, Ping
Patel, Tulsi
Jang, Sumin
Hammelman, Jennifer
De Nooij, Joriene C
Kopunova, Rachel
Mazzoni, Esteban O
Ruan, Yijun
Date Issued
2022
Journal
Neuron
Publisher
Elsevier BV
Citation
Closser, Michael, Guo, Yuchun, Wang, Ping, Patel, Tulsi, Jang, Sumin et al. 2022. "An expansion of the non-coding genome and its regulatory potential underlies vertebrate neuronal diversity." Neuron, 110 (1).
Version
Author's final manuscript
Abstract
Proper assembly and function of the nervous system requires the generation of a uniquely diverse population of neurons expressing a cell-type-specific combination of effector genes that collectively define neuronal morphology, connectivity, and function. How countless partially overlapping but cell-type-specific patterns of gene expression are controlled at the genomic level remains poorly understood. Here we show that neuronal genes are associated with highly complex gene regulatory systems composed of independent cell-type- and cell-stage-specific regulatory elements that reside in expanded non-coding genomic domains. Mapping enhancer-promoter interactions revealed that motor neuron enhancers are broadly distributed across the large chromatin domains. This distributed regulatory architecture is not a unique property of motor neurons but is employed throughout the nervous system. The number of regulatory elements increased dramatically during the transition from invertebrates to vertebrates, suggesting that acquisition of new enhancers might be a fundamental process underlying the evolutionary increase in cellular complexity.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.NEURON.2021.10.014
