Exploiting genetic variation to uncover rules of transcription factor binding and chromatin accessibility

Vivek Behera, Perry Evans, Carolyne J. Face, Nicole Hamagami, Laavanya Sankaranarayanan, Cheryl A. Keller, Belinda Giardine, Kai Tan, Ross C. Hardison, Junwei Shi and Gerd A. Blobel ()
Additional contact information
Vivek Behera: University of Pennsylvania
Perry Evans: Children’s Hospital of Philadelphia
Carolyne J. Face: Children’s Hospital of Philadelphia
Nicole Hamagami: Children’s Hospital of Philadelphia
Laavanya Sankaranarayanan: Children’s Hospital of Philadelphia
Cheryl A. Keller: Penn State University
Belinda Giardine: Penn State University
Kai Tan: Children’s Hospital of Philadelphia
Ross C. Hardison: Penn State University
Junwei Shi: University of Pennsylvania
Gerd A. Blobel: Children’s Hospital of Philadelphia

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract Single-nucleotide variants that underlie phenotypic variation can affect chromatin occupancy of transcription factors (TFs). To delineate determinants of in vivo TF binding and chromatin accessibility, we introduce an approach that compares ChIP-seq and DNase-seq data sets from genetically divergent murine erythroid cell lines. The impact of discriminatory single-nucleotide variants on TF ChIP signal enables definition at single base resolution of in vivo binding characteristics of nuclear factors GATA1, TAL1, and CTCF. We further develop a facile complementary approach to more deeply test the requirements of critical nucleotide positions for TF binding by combining CRISPR-Cas9-mediated mutagenesis with ChIP and targeted deep sequencing. Finally, we extend our analytical pipeline to identify nearby contextual DNA elements that modulate chromatin binding by these three TFs, and to define sequences that impact kb-scale chromatin accessibility. Combined, our approaches reveal insights into the genetic basis of TF occupancy and their interplay with chromatin features.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-03082-6 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:9:y:2018:i:1:d:10.1038_s41467-018-03082-6

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

DOI: 10.1038/s41467-018-03082-6

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 ().