ZBTB2 as a novel reader for unmethylated DNA [RNA-seq]

DNA methylation is a dynamic epigenetic modification that plays a key role in various cellular processes. Proteins that bind to DNA depending on its methylation status are thought to play an important role in DNA methylation-mediated gene expression. Using a variety of genomics and proteomics approaches, we identified ZBTB2 as a novel reader of unmethylated DNA. ZBTB2, which forms a complex with ZBTB25 and ZNF639, preferentially binds at CpG island promoters in mouse embryonic stem cells, from where it regulates genes that are involved in the exit from pluripotency. Binding of ZBTB2 to target genes is mostly associated with gene activation. Furthermore, ZBTB2 is intricately interwoven with DNA methylation, as we found not only that its binding to DNA is methylation-sensitive, but also that ZBTB2 regulates the turnover of methylated DNA. Summarising, we propose that ZBTB2 is a DNA methylation-sensitive transcription factor that is involved in cellular differentiation. Overall design: RNA-seq samples of wildtype ESCs and Zbtb2 KO ESCs

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Karemaker ID, Vermeulen M