Abstract
BackgroundCGGBP1 is a repetitive DNA-binding transcription regulator with target sites at CpG-rich sequences such as CGG repeats and Alu-SINEs and L1-LINEs. The role of CGGBP1 as a possible mediator of CpG methylation however remains unknown. At CpG-rich sequences cytosine methylation is a major mechanism of transcriptional repression. Concordantly, gene-rich regions typically carry lower levels of CpG methylation than the repetitive elements. It is well known that at interspersed repeats Alu-SINEs and L1-LINEs high levels of CpG methylation constitute a transcriptional silencing and retrotransposon inactivating mechanism.ResultsHere, we have studied genome-wide CpG methylation with or without CGGBP1-depletion. By high throughput sequencing of bisulfite-treated genomic DNA we have identified CGGBP1 to be a negative regulator of CpG methylation at repetitive DNA sequences. In addition, we have studied CpG methylation alterations on Alu and L1 retrotransposons in CGGBP1-depleted cells using a novel bisulfite-treatment and high throughput sequencing approach.ConclusionsThe results clearly show that CGGBP1 is a possible bidirectional regulator of CpG methylation at Alus, and acts as a repressor of methylation at L1 retrotransposons.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1593-2) contains supplementary material, which is available to authorized users.
Highlights
CGGBP1 is a repetitive DNA-binding transcription regulator with target sites at CpG-rich sequences such as CGG repeats and Alu-SINEs and L1-LINEs
1064Sk cells were transduced with control or CGGBP1targeting shmiR-lentiviruses and CGGBP1-depletion was confirmed by western blotting (Additional file 1)
The results showed that cytosine methylation was increased upon CGGBP1 depletion (Figure 1A; Ratio paired T test p=0.0211)
Summary
CGGBP1 is a repetitive DNA-binding transcription regulator with target sites at CpG-rich sequences such as CGG repeats and Alu-SINEs and L1-LINEs. The role of CGGBP1 as a possible mediator of CpG methylation remains unknown. It is well known that at interspersed repeats Alu-SINEs and L1-LINEs high levels of CpG methylation constitute a transcriptional silencing and retrotransposon inactivating mechanism. The CpG-richness of CGGBP1-binding sequences raises the question whether CpG methylation may be a mechanism underlying transcription-regulation by CGGBP1. Despite evidence of transcriptional silencing by binding of CGGBP1 to unmethylated CGG repeats [2,4], the effects of CGGBP1 on CpG methylation have never been studied. Unlike the gene-rich regions, the repetitive DNA e.g. peri-centromeric, sub-telomeric and satellite repeats as well as interspersed repeats, including Alu and LINE-1 elements carry high methylation levels [6,7,8]
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