Title

An expansion of the non-coding genome and its regulatory potential underlies vertebrate neuronal diversity.

Document Type

Article

Publication Date

1-5-2022

Publication Title

Neuron

Keywords

JGM

JAX Source

Neuron 2022 Jan 5; 110:1-16

ISSN

1097-4199

PMID

34727520

DOI

https://doi.org/10.1016/j.neuron.2021.10.014

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.

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