Whether and how DNA methylation influences the binding of transcription factors (TFs) to their corresponding DNA sequence motifs in vivo remains largely unresolved. In a recent publication, Schübeler and co‐workers (Domcke et al, 2015) identify a few methylation‐restricted TFs in mouse embryonic stem cells, including NRF1. The authors show that NRF1 binding to its motif can be outcompeted by de novo DNA methylation, suggesting that methylation‐sensitive TFs rely on neighbouring motifs in cis—bound by pioneer TFs—to ensure local hypomethylation.
See also: S Domcke et al (December 2015)
Although all cells of an adult eukaryotic organism harbour the same DNA content, they constitute a multitude of different cell types. This phenotypical diversity is achieved by cell type‐specific gene expression programmes; how this differential gene expression is regulated remains an active area of research. Transcription factors (TFs) play an important role in regulating gene expression by binding to their corresponding DNA sequence motifs and thereby regulating transcription of nearby genes. TF–DNA interactions have been studied extensively in vitro, uncovering various contributing factors such as the presence of cofactors, chromatin accessibility and DNA methylation (reviewed in Slattery et al, 2014). However, TFs only bind to a subset of their motifs in vivo. The mechanisms behind this selectivity remain largely unresolved, as it has thus far proven difficult to directly translate the knowledge obtained in in vitro experiments to the in vivo situation (Slattery …
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