Landscape of allele-specific transcription factor binding in the human genome

Sergey Abramov, Alexandr Boytsov, Daria Bykova, Dmitry D. Penzar, Ivan Yevshin, Semyon K. Kolmykov, Marina V. Fridman, Alexander V. Favorov, Ilya E. Vorontsov, Eugene Baulin, Fedor Kolpakov, Vsevolod J. Makeev () and Ivan V. Kulakovskiy ()
Additional contact information
Sergey Abramov: Russian Academy of Sciences
Alexandr Boytsov: Russian Academy of Sciences
Daria Bykova: Lomonosov Moscow State University
Dmitry D. Penzar: Russian Academy of Sciences
Ivan Yevshin: Federal Research Center for Information and Computational Technologies
Semyon K. Kolmykov: Federal Research Center for Information and Computational Technologies
Marina V. Fridman: Russian Academy of Sciences
Alexander V. Favorov: Russian Academy of Sciences
Ilya E. Vorontsov: Russian Academy of Sciences
Eugene Baulin: Moscow Institute of Physics and Technology
Fedor Kolpakov: Federal Research Center for Information and Computational Technologies
Vsevolod J. Makeev: Russian Academy of Sciences
Ivan V. Kulakovskiy: Russian Academy of Sciences

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Sequence variants in gene regulatory regions alter gene expression and contribute to phenotypes of individual cells and the whole organism, including disease susceptibility and progression. Single-nucleotide variants in enhancers or promoters may affect gene transcription by altering transcription factor binding sites. Differential transcription factor binding in heterozygous genomic loci provides a natural source of information on such regulatory variants. We present a novel approach to call the allele-specific transcription factor binding events at single-nucleotide variants in ChIP-Seq data, taking into account the joint contribution of aneuploidy and local copy number variation, that is estimated directly from variant calls. We have conducted a meta-analysis of more than 7 thousand ChIP-Seq experiments and assembled the database of allele-specific binding events listing more than half a million entries at nearly 270 thousand single-nucleotide polymorphisms for several hundred human transcription factors and cell types. These polymorphisms are enriched for associations with phenotypes of medical relevance and often overlap eQTLs, making candidates for causality by linking variants with molecular mechanisms. Specifically, there is a special class of switching sites, where different transcription factors preferably bind alternative alleles, thus revealing allele-specific rewiring of molecular circuitry.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-23007-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23007-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-23007-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().