Quantitative Analysis of the DNA Methylation Sensitivity of Transcription Factor Complexes.

ABSTRACT: Although DNA modifications play an important role in gene regulation, the underlying mechanisms remain elusive. We developed EpiSELEX-seq to probe the sensitivity of transcription factor binding to DNA modification in vitro using massively parallel sequencing. Feature-based modeling quantifies the effect of cytosine methylation (⁵mC) on binding free energy in a position-specific manner. Application to the human bZIP proteins ATF4 and C/EBPβ and three different Pbx-Hox complexes shows that ⁵mCpG can both increase and decrease affinity, depending on where the modification occurs within the protein-DNA interface. The TF paralogs tested vary in their methylation sensitivity, for which we provide a structural rationale. We show that ⁵mCpG can also enhance in vit

SUBMITTER: Kribelbauer JF 

PROVIDER: S-EPMC5533174 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature