title: CGGBP1 mitigates cytosine methylation at repetitive DNA sequences.
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.
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Science for Life Laboratory, Rudbeck Laboratory, Dag Hammarskjölds Väg 20, Uppsala, 75185, Sweden. prasoon.agarwal@igp.uu.se.
authors.forename: Prasoon
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: EMBL, Core Facilities and Services, Meyerhofsstrasse 1, Heidelberg, D-69117, Germany. collier@embl.de.
authors.forename: Paul
authors.initials: P
authors.lastname: Collier
authors.affiliation: EMBL, Core Facilities and Services, Meyerhofsstrasse 1, Heidelberg, D-69117, Germany. fritz@embl.de.
authors.forename: Markus Hsi-Yang
authors.initials: MH
authors.lastname: Fritz
authors.affiliation: EMBL, Core Facilities and Services, Meyerhofsstrasse 1, Heidelberg, D-69117, Germany. benes@embl.de.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Benes
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Science for Life Laboratory, Rudbeck Laboratory, Dag Hammarskjölds Väg 20, Uppsala, 75185, Sweden. helena.jernberg_wiklund@igp.uu.se.
authors.forename: Helena Jernberg
authors.initials: HJ
authors.lastname: Wiklund
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Science for Life Laboratory, Rudbeck Laboratory, Dag Hammarskjölds Väg 20, Uppsala, 75185, Sweden. bengt.westermark@igp.uu.se.
authors.forename: Bengt
authors.initials: B
authors.lastname: Westermark
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Science for Life Laboratory, Rudbeck Laboratory, Dag Hammarskjölds Väg 20, Uppsala, 75185, Sweden. umashankar.singh@igp.uu.se.
authors.forename: Umashankar
authors.initials: U
authors.lastname: Singh
mesh_terms: D020087:Alu Elements / Q000235:genetics; D002460:Cell Line; D018899:CpG Islands / Q000235:genetics; D003596:Cytosine / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D012091:Repetitive Sequences, Nucleic Acid; D018626:Retroelements / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: C106905:CGGBP1 protein, human; D004268:DNA-Binding Proteins; D018626:Retroelements; D003596:Cytosine; D004247:DNA