RRC ID 53326
著者 Lussi YC, Mariani L, Friis C, Peltonen J, Myers TR, Krag C, Wong G, Salcini AE.
タイトル Impaired removal of H3K4 methylation affects cell fate determination and gene transcription.
ジャーナル Development
Abstract Methylation of histone 3 lysine 4 (H3K4) is largely associated with promoters and enhancers of actively transcribed genes and is finely regulated during development by the action of histone methyltransferases and demethylases. H3K4me3 demethylases of the KDM5 family have been previously implicated in development, but how the regulation of H3K4me3 level controls developmental processes is not fully established. Here, we show that the H3K4 demethylase RBR-2, the unique member of the KDM5 family in C. elegans, acts cell-autonomously and in a catalytic-dependent manner to control vulva precursor cells fate acquisition, by promoting the LIN-12/Notch pathway. Using genome-wide approaches, we show that RBR-2 reduces the H3K4me3 level at transcription start sites (TSSs) and in regions upstream of the TSSs, and acts both as a transcription repressor and activator. Analysis of the lin-11 genetic locus, a direct RBR-2 target gene required for vulva precursor cell fate acquisition, shows that RBR-2 controls the epigenetic signature of the lin-11 vulva-specific enhancer and lin-11 expression, providing in vivo evidence that RBR-2 can positively regulate transcription and cell fate acquisition by controlling enhancer activity.
巻・号 143(20)
ページ 3751-3762
公開日 2016-10-15
DOI 10.1242/dev.139139
PII dev.139139
PMID 27578789
MeSH Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Differentiation / genetics Cell Differentiation / physiology Gene Expression Regulation, Developmental / genetics Gene Expression Regulation, Developmental / physiology Histone Methyltransferases Histone-Lysine N-Methyltransferase / genetics Histone-Lysine N-Methyltransferase / metabolism* Histones Homeodomain Proteins / genetics Homeodomain Proteins / metabolism Methylation Promoter Regions, Genetic / genetics Retinoblastoma-Binding Protein 2 / genetics Retinoblastoma-Binding Protein 2 / metabolism
IF 5.611
引用数 7
リソース情報
線虫 tm3141 tm1231