Survey of variation in human transcription factors reveals prevalent DNA binding changes.
Journal Article (Journal Article)
Sequencing of exomes and genomes has revealed abundant genetic variation affecting the coding sequences of human transcription factors (TFs), but the consequences of such variation remain largely unexplored. We developed a computational, structure-based approach to evaluate TF variants for their impact on DNA binding activity and used universal protein-binding microarrays to assay sequence-specific DNA binding activity across 41 reference and 117 variant alleles found in individuals of diverse ancestries and families with Mendelian diseases. We found 77 variants in 28 genes that affect DNA binding affinity or specificity and identified thousands of rare alleles likely to alter the DNA binding activity of human sequence-specific TFs. Our results suggest that most individuals have unique repertoires of TF DNA binding activities, which may contribute to phenotypic variation.
Full Text
Duke Authors
Cited Authors
- Barrera, LA; Vedenko, A; Kurland, JV; Rogers, JM; Gisselbrecht, SS; Rossin, EJ; Woodard, J; Mariani, L; Kock, KH; Inukai, S; Siggers, T; Shokri, L; Gordân, R; Sahni, N; Cotsapas, C; Hao, T; Yi, S; Kellis, M; Daly, MJ; Vidal, M; Hill, DE; Bulyk, ML
Published Date
- March 25, 2016
Published In
Volume / Issue
- 351 / 6280
Start / End Page
- 1450 - 1454
PubMed ID
- 27013732
Pubmed Central ID
- PMC4825693
Electronic International Standard Serial Number (EISSN)
- 1095-9203
Digital Object Identifier (DOI)
- 10.1126/science.aad2257
Language
- eng
Conference Location
- United States