CGGBP1 mitigates cytosine methylation at repetitive DNA sequences

• Published in: BMC genomics Vol. 16; no. 1; p. 390
• Main Authors: Agarwal, Prasoon, Collier, Paul, Fritz, Markus Hsi-Yang, Benes, Vladimir, Wiklund, Helena Jernberg, Westermark, Bengt, Singh, Umashankar
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 16.05.2015; BioMed Central
• Subjects: Alu Elements - genetics; Analysis; Cell Line; CpG Islands - genetics; Cytosine - chemistry; Cytosine - metabolism; DNA - chemistry; DNA - metabolism; DNA Methylation - genetics; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Genes; Genetic aspects; Genetic transcription; High-Throughput Nucleotide Sequencing; Humans; Repetitive Sequences, Nucleic Acid; Retroelements - genetics; Sequence Analysis, DNA
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-015-1593-2

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 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. Here, 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. The 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.