RRC ID 40100
Author Mariani L, Lussi YC, Vandamme J, Riveiro A, Salcini AE.
Title The H3K4me3/2 histone demethylase RBR-2 controls axon guidance by repressing the actin-remodeling gene wsp-1.
Journal Development
Abstract 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 H3K4me3/2 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, and 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.
Volume 143(5)
Pages 851-63
Published 2016-3-1
DOI 10.1242/dev.132985
PII dev.132985
PMID 26811384
MeSH Actins / metabolism* Alleles Animals Axons / physiology* Body Patterning Caenorhabditis elegans Caenorhabditis elegans Proteins / physiology* Catalysis Chromatin / metabolism Chromosomal Proteins, Non-Histone / physiology* Epigenesis, Genetic Gene Expression Regulation, Developmental* Histone Demethylases / metabolism Histones / metabolism* Lysine / metabolism Methylation Microscopy, Fluorescence Mutation Neurons / metabolism Protein Structure, Tertiary Retinoblastoma-Binding Protein 2 / physiology* Signal Transduction Transgenes
IF 5.611
Times Cited 7
WOS Category DEVELOPMENTAL BIOLOGY
Resource
C.elegans tm3141 tm1231 tm2530 tm3980 tm3713 tm472