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Impaired removal of H3K4 methylation affects cell fate determination and gene transcription
Lussi Y.C.1; Mariani L.1; Friis C.1; Peltonen J.2; Myers T.R.1; Krag C.1; Wong G.2; Salcini A.E.1
2016-10-15
Source PublicationDevelopment (Cambridge)
ISSN14779129 09501991
Volume143Issue:20Pages:3751-3762
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.

KeywordC. Elegans Enhancer Gene Transcription H3k4 Methylation Kdm5 Rbr-2 Vpc Differentiation
DOI10.1242/dev.139139
URLView the original
Indexed BySCI
Language英语
WOS Research AreaDevelopmental Biology
WOS SubjectDevelopmental Biology
WOS IDWOS:000393452500011
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Cited Times [WOS]:5   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Københavns Universitet
2.Itä-Suomen yliopisto
3.Universidade de Macau
Recommended Citation
GB/T 7714
Lussi Y.C.,Mariani L.,Friis C.,et al. Impaired removal of H3K4 methylation affects cell fate determination and gene transcription[J]. Development (Cambridge),2016,143(20):3751-3762.
APA Lussi Y.C..,Mariani L..,Friis C..,Peltonen J..,Myers T.R..,...&Salcini A.E..(2016).Impaired removal of H3K4 methylation affects cell fate determination and gene transcription.Development (Cambridge),143(20),3751-3762.
MLA Lussi Y.C.,et al."Impaired removal of H3K4 methylation affects cell fate determination and gene transcription".Development (Cambridge) 143.20(2016):3751-3762.
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