The Genetics of Transcription Factor DNA Binding Variation.
- Deplancke B Laboratory of Systems Biology and Genetics, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland. Electronic address: bart.deplancke@epfl.ch.
- Alpern D Laboratory of Systems Biology and Genetics, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
- Gardeux V Laboratory of Systems Biology and Genetics, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
- 2016-07-30
Published in:
- Cell. - 2016
English
Most complex trait-associated variants are located in non-coding regulatory regions of the genome, where they have been shown to disrupt transcription factor (TF)-DNA binding motifs. Variable TF-DNA interactions are therefore increasingly considered as key drivers of phenotypic variation. However, recent genome-wide studies revealed that the majority of variable TF-DNA binding events are not driven by sequence alterations in the motif of the studied TF. This observation implies that the molecular mechanisms underlying TF-DNA binding variation and, by extrapolation, inter-individual phenotypic variation are more complex than originally anticipated. Here, we summarize the findings that led to this important paradigm shift and review proposed mechanisms for local, proximal, or distal genetic variation-driven variable TF-DNA binding. In addition, we discuss the biomedical implications of these findings for our ability to dissect the molecular role(s) of non-coding genetic variants in complex traits, including disease susceptibility.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1016/j.cell.2016.07.012
- PMID 27471964
- Persistent URL
- https://sonar.ch/global/documents/190440
Statistics
Document views: 12
File downloads:
- fulltext.pdf: 0