转录因子
生物
亲缘关系
染色质
DNA结合位点
遗传学
结合位点
DNA结合蛋白
抄写(语言学)
发起人
计算生物学
DNA
基因
基因表达
生物化学
语言学
哲学
作者
Hannah K. Neikes,Katarzyna Kliza,Cathrin Gräwe,Roelof A. Wester,Pascal W.T.C. Jansen,Lieke A. Lamers,Marijke P. Baltissen,Simon J. van Heeringen,Colin Logie,Sarah A. Teichmann,Rik G.H. Lindeboom,Michiel Vermeulen
标识
DOI:10.1038/s41587-023-01715-w
摘要
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.
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