CGGBP1 mitigates cytosine methylation at repetitive DNA sequences

BMC Genomics. 2015 May 16;16(1):390. doi: 10.1186/s12864-015-1593-2.

Abstract

Background: 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.

Results: 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.

Conclusions: 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.

MeSH terms

  • Alu Elements / genetics
  • 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*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Repetitive Sequences, Nucleic Acid*
  • Retroelements / genetics
  • Sequence Analysis, DNA

Substances

  • CGGBP1 protein, human
  • DNA-Binding Proteins
  • Retroelements
  • Cytosine
  • DNA