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ZBTB 2 reads unmethylated CpG island promoters and regulates embryonic stem cell differentiation
Author(s) -
Karemaker Ino D,
Vermeulen Michiel
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201744993
Subject(s) - library science , biology , computational biology , computer science
Proteins that bind to DNA depending on its methylation status play an important role in methylation‐mediated regulation of gene expression. Using a variety of genomics and proteomics approaches, we identify zinc finger and BTB domain‐containing protein 2 ( ZBTB 2) as a reader of unmethylated DNA in mouse embryonic stem cells. ZBTB 2 preferentially binds to CpG island promoters, where it acts as a transcriptional activator. The binding of ZBTB 2 to its targets is direct and independent of two other zinc finger proteins, ZBTB 25 and ZNF 639, which we show to interact with ZBTB 2. Our data suggest an anticorrelation between ZBTB 2 DNA binding and DNA methylation, indicating that ZBTB 2‐binding dynamics in vivo are sensitive to differential DNA methylation. ZBTB 2 is intricately interwoven with DNA methylation, as we find not only that its binding to DNA is methylation sensitive, but also that ZBTB 2 regulates the turnover of methylated DNA . In ZBTB 2 knockout cells, several pluripotency factors are upregulated, inducing a delay in differentiation. We propose that ZBTB 2 is a novel DNA methylation‐sensitive transcription factor that regulates cellular differentiation.