HomeHome

Quantitative Analysis of the DNA Methylation Sensitivity of Transcription Factor Complexes

Judith F. Kribelbauer; Oleg Laptenko; Siying Chen; Gabriella D. Martini; William Allen Freed-Pastor; Carol L. Prives; Richard S. Mann; Harmen J. Bussemaker

Title:
Quantitative Analysis of the DNA Methylation Sensitivity of Transcription Factor Complexes
Author(s):
Kribelbauer, Judith F.
Laptenko, Oleg
Chen, Siying
Martini, Gabriella D.
Freed-Pastor, William Allen
Prives, Carol L.
Mann, Richard S.
Bussemaker, Harmen J.
Date:
Type:
Articles
Department(s):
Biological Sciences
Systems Biology
Biochemistry and Molecular Biophysics
Volume:
19
Persistent URL:
Book/Journal Title:
Cell Reports
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 vitro p53 binding and provide evidence for increased in vivo p53 occupancy at methylated binding sites, correlating with primed enhancer histone marks. Our results establish a powerful strategy for dissecting the epigenomic modulation of protein-DNA interactions and their role in gene regulation.
Subject(s):
DNA--Methylation
Transcription factors
Genetic regulation
DNA-protein interactions
Epigenetics
Publisher DOI:
https://doi.org/10.1016/j.celrep.2017.05.069
Item views
16
Metadata:
text | xml
Suggested Citation:
Judith F. Kribelbauer, Oleg Laptenko, Siying Chen, Gabriella D. Martini, William Allen Freed-Pastor, Carol L. Prives, Richard S. Mann, Harmen J. Bussemaker, , Quantitative Analysis of the DNA Methylation Sensitivity of Transcription Factor Complexes, Columbia University Academic Commons, .

Columbia University Libraries | Policies | FAQ