title: The recently identified modifier of murine metastable epialleles, Rearranged L-Myc Fusion, is involved in maintaining epigenetic marks at CpG island shores and enhancers.
abstract: BACKGROUND
  We recently identified a novel protein, Rearranged L-myc fusion (Rlf), that is required for DNA hypomethylation and transcriptional activity at two specific regions of the genome known to be sensitive to epigenetic gene silencing. To identify other loci affected by the absence of Rlf, we have now analysed 12 whole genome bisulphite sequencing datasets across three different embryonic tissues/stages from mice wild-type or null for Rlf.
  
  
  RESULTS
  Here we show that the absence of Rlf results in an increase in DNA methylation at thousands of elements involved in transcriptional regulation and many of the changes occur at enhancers and CpG island shores. ChIP-seq for H3K4me1, a mark generally found at regulatory elements, revealed associated changes at many of the regions that are differentially methylated in the Rlf mutants. RNA-seq showed that the numerous effects of the absence of Rlf on the epigenome are associated with relatively subtle effects on the mRNA population. In vitro studies suggest that Rlf's zinc fingers have the capacity to bind DNA and that the protein interacts with other known epigenetic modifiers.
  
  
  CONCLUSIONS
  This study provides the first evidence that the epigenetic modifier Rlf is involved in the maintenance of DNA methylation at enhancers and CGI shores across the genome.
authors: Sarah K
authors: SK
authors: Harten
authors: Harald
authors: H
authors: Oey
authors: Lauren M
authors: LM
authors: Bourke
authors: Vandhana
authors: V
authors: Bharti
authors: Luke
authors: L
authors: Isbel
authors: Lucia
authors: L
authors: Daxinger
authors: Pierre
authors: P
authors: Faou
authors: Neil
authors: N
authors: Robertson
authors: Jacqueline M
authors: JM
authors: Matthews
authors: Emma
authors: E
authors: Whitelaw
mesh_terms: D000483:Alleles; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D044127:Epigenesis, Genetic; D005091:Exons / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D060045:Genes, Modifier; D056426:Genetic Loci; D020662:Guanine Nucleotide Exchange Factors; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D020662:Guanine Nucleotide Exchange Factors; D006657:Histones; C490805:Rgl2 protein, mouse; D014157:Transcription Factors; D004247:DNA; D008239:Lysine