The H3K4me3/2 histone demethylase RBR-2 controls axon guidance by repressing the actin-remodeling gene wsp-1
| Autor: | Anna Elisabetta Salcini, Luca Mariani, Alba Redo Riveiro, Yvonne C. Lussi, Julien Vandamme |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
NURF complex Chromosomal Proteins Non-Histone Regulator H3K4 methylation Methylation Catalysis Epigenesis Genetic Histones 03 medical and health sciences Animals Transgenes Epigenetics Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Alleles Body Patterning Histone Demethylases Neurons Histone demethylase biology Lysine Axon guidance Gene Expression Regulation Developmental Actin remodeling Cell Biology Molecular biology Actins Axons Chromatin Protein Structure Tertiary Cell biology 030104 developmental biology Histone Microscopy Fluorescence Mutation biology.protein C. elegans Demethylase H3K4me3 Neuronal development Retinoblastoma-Binding Protein 2 Signal Transduction Developmental Biology |
| Zdroj: | Mariani, L, Lussi, Y C, Vandamme, J, Riveiro, A & Salcini, A E 2016, ' The H3K4me3/2 histone demethylase RBR-2 controls axon guidance by repressing the actin-remodeling gene wsp-1 ', Development, vol. 143, no. 5, pp. 851-863 . https://doi.org/10.1242/dev.132985 |
| Popis: | The dynamic regulation of histone modifications is important for modulating transcriptional programs during development. Aberrant H3K4 methylation is associated with neurological disorders, but how the levels and the recognition of this modification affect specific neuronal processes is unclear. Here we show that RBR-2, the sole homolog of the KDM5 family of H3K4me3/me2 demethylases in Caenorhabditis elegans, ensures correct axon guidance by controlling the expression of the actin regulator wsp-1. Loss of rbr-2 results in increased levels of H3K4me3 at the transcriptional start site of wsp-1, with concomitant higher wsp-1 expression responsible for defective axon guidance. In agreement, overexpression of WSP-1 mimics rbr-2 loss, while its depletion restores normal axon guidance in rbr-2 mutants. NURF-1, an H3K4me3-binding protein and member of the chromatin-remodeling complex NURF, is required for promoting aberrant wsp-1 transcription in rbr-2 mutants and its ablation restores wild type expression of wsp-1 and axon guidance. Thus, our results establish a precise role for epigenetic regulation in neuronal development by demonstrating a functional link between RBR-2 activity, H3K4me3 levels, the NURF complex and the expression of WSP-1. |
| Databáze: | OpenAIRE |
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