Regulators of H3K4 methylation mutated in neurodevelopmental disorders control axon guidance in Caenorhabditis elegans.

Development
Steffen Abay-NørgaardAnna Elisabetta Salcini

Abstract

Post-translational histone modifications regulate chromatin compaction and gene expression to control many aspects of development. Mutations in genes encoding regulators of H3K4 methylation are causally associated with neurodevelopmental disorders characterized by intellectual disability and deficits in motor functions. However, it remains unclear how H3K4 methylation influences nervous system development and contributes to the aetiology of disease. Here, we show that the catalytic activity of set-2, the Caenorhabditis elegans homologue of the H3K4 methyltransferase KMT2F/G (SETD1A/B) genes, controls embryonic transcription of neuronal genes and is required for establishing proper axon guidance, and for neuronal functions related to locomotion and learning. Moreover, we uncover a striking correlation between components of the H3K4 regulatory machinery mutated in neurodevelopmental disorders and the process of axon guidance in C. elegans Thus, our study supports an epigenetic-based model for the aetiology of neurodevelopmental disorders, based on an aberrant axon guidance process originating from deregulated H3K4 methylation.

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Citations

Dec 18, 2020·The FEBS Journal·Carlos Wilson, Alfredo Cáceres
Feb 26, 2021·Neural Plasticity·Huixia GengLai Wang
Aug 5, 2021·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Marjolein J A WeertsTahsin Stefan Barakat

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Methods Mentioned

BETA
transgenic
PCA
Profiler
PCR

Software Mentioned

DESeq2
GraphPad Prism
COMPASS
ImageJ
Profiler

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