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

Harten, Sarah K., Oey, Harald, Bourke, Lauren M., Bharti, Vandhana, Isbel, Luke, Daxinger, Lucia, Faou, Pierre, Robertson, Neil, Matthews, Jacqueline M. and Whitelaw, Emma (2015) 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, 13 21: 1-15. doi:10.1186/s12915-015-0128-2


Author Harten, Sarah K.
Oey, Harald
Bourke, Lauren M.
Bharti, Vandhana
Isbel, Luke
Daxinger, Lucia
Faou, Pierre
Robertson, Neil
Matthews, Jacqueline M.
Whitelaw, Emma
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
Journal name BMC Biology   Check publisher's open access policy
ISSN 1741-7007
Publication date 2015-03-26
Year available 2015
Sub-type Article (original research)
DOI 10.1186/s12915-015-0128-2
Open Access Status DOI
Volume 13
Issue 21
Start page 1
End page 15
Total pages 15
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted 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.

Conclusion

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.
Keyword Rearranged L-Myc Fusion
Rlf
DNA methylation
Enhancers
Bisulphite
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Wed, 29 Jun 2016, 14:03:39 EST by Harald Oey on behalf of UQ Diamantina Institute