The recently identified modifier of murine metastable epialleles, Rearranged L-Myc Fusion, is involved in maintaining epigenetic marks at CpG island shores and enhancers

BMC Biology

Research Article

Pierre Faou¹  Harald Oey²  Luke Isbel²  Emma Whitelaw²  Lucia Daxinger³  Vandhana Bharti⁴  Sarah K Harten⁴  Lauren M Bourke⁵  Neil Robertson⁶  Jacqueline M Matthews⁶ 

[1] Department of Biochemistry, La Trobe University, 3086, Melbourne, VIC, Australia;Department of Genetics, La Trobe Institute for Molecular Science, La Trobe University, 3086, Bundoora, Melbourne, VIC, Australia;Department of Genetics, La Trobe Institute for Molecular Science, La Trobe University, 3086, Bundoora, Melbourne, VIC, Australia;Present Address: Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands;Epigenetics Laboratory, QIMR Berghofer Medical Research Institute, 4006, Herston, Brisbane, QLD, Australia;Epigenetics Laboratory, QIMR Berghofer Medical Research Institute, 4006, Herston, Brisbane, QLD, Australia;School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Australia;School of Molecular Bioscience, University of Sydney, 2006, Sydney, NSW, Australia;

关键词: Rearranged L-Myc Fusion;    Rlf;    DNA methylation;    Enhancers;    Bisulphite;   

DOI  :  10.1186/s12915-015-0128-2

 received in 2014-12-15, accepted in 2015-02-23,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundWe 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.ResultsHere 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.ConclusionThis 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.

【 授权许可】

Unknown   
© Harten et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.