Quantification of absolute transcription factor binding affinities in the native chromatin context using BANC-seq.

Publisher: Nature America Publishing Country of Publication: United States NLM ID: 9604648 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1696 (Electronic) Linking ISSN: 10870156 NLM ISO Abbreviation: Nat Biotechnol Subsets: MEDLINE

Publication: New York Ny : Nature America Publishing
Original Publication: New York, NY : Nature Pub. Co., [1996-

Chromatin*/genetics ; Transcription Factors*/genetics ; Transcription Factors*/metabolism; Protein Binding ; DNA/genetics ; DNA/metabolism ; Gene Expression Regulation ; Binding Sites/genetics ; Sequence Analysis, DNA

Transcription factor binding across the genome is regulated by DNA sequence and chromatin features. However, it is not yet possible to quantify the impact of chromatin context on transcription factor binding affinities. Here, we report a method called binding affinities to native chromatin by sequencing (BANC-seq) to determine absolute apparent binding affinities of transcription factors to native DNA across the genome. In BANC-seq, a concentration range of a tagged transcription factor is added to isolated nuclei. Concentration-dependent binding is then measured per sample to quantify apparent binding affinities across the genome. BANC-seq adds a quantitative dimension to transcription factor biology, which enables stratification of genomic targets based on transcription factor concentration and prediction of transcription factor binding sites under non-physiological conditions, such as disease-associated overexpression of (onco)genes. Notably, whereas consensus DNA binding motifs for transcription factors are important to establish high-affinity binding sites, these motifs are not always strictly required to generate nanomolar-affinity interactions in the genome.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Comment in: Nat Genet. 2023 May;55(5):727. doi: 10.1038/s41588-023-01407-w. (PMID: 37173528)

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9007-49-2 (DNA)

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