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Gustems, M. ; Woellmer, A. ; Rothbauer, U.* ; Eck, S.H. ; Wieland, T. ; Lutter, D. ; Hammerschmidt, W.

c-Jun/c-Fos heterodimers regulate cellular genes via a newly identified class of methylated DNA sequence motifs.

Nucleic Acids Res. 42, 3059-3072 (2014)
Publ. Version/Full Text Volltext DOI PMC
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CpG methylation in mammalian DNA is known to interfere with gene expression by inhibiting the binding of transactivators to their cognate sequence motifs or recruiting proteins involved in gene repression. An Epstein-Barr virus-encoded transcription factor, Zta, was the first example of a sequence-specific transcription factor that preferentially recognizes and selectively binds DNA sequence motifs with methylated CpG residues, reverses epigenetic silencing and activates gene transcription. The DNA binding domain of Zta is homologous to c-Fos, a member of the cellular AP-1 (activator protein 1) transcription factor family, which regulates cell proliferation and survival, apoptosis, transformation and oncogenesis. We have identified a novel AP-1 binding site termed meAP-1, which contains a CpG dinucleotide. If methylated, meAP-1 sites are preferentially bound by the AP-1 heterodimer c-Jun/c-Fos in vitro and in cellular chromatin in vivo. In activated human primary B cells, c-Jun/c-Fos locates to these methylated elements in promoter regions of transcriptionally activated genes. Reminiscent of the viral Zta protein, c-Jun/c-Fos is the first identified cellular member of the AP-1 family of transactivators that can induce expression of genes with methylated, hence repressed promoters, reversing epigenetic silencing.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Epstein-barr-virus; Chip-seq Data; Cpg Methylation; Binding-sites; Viral Genome; Transcriptional Activation; Protein Complexes; Ap-1 Site; Cells; Recognition
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Journal Nucleic Acids Research
Quellenangaben Volume: 42, Issue: 5, Pages: 3059-3072 Article Number: , Supplement: ,
Publisher Oxford University Press
Publishing Place Oxford
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)
Institute of Human Genetics (IHG)
Institute of Diabetes and Obesity (IDO)