Student and Faculty Publications
Publication Date
9-15-2022
Journal
Molecular Cell
Abstract
Regulatory elements activate promoters by recruiting transcription factors (TFs) to specific motifs. Notably, TF-DNA interactions often depend on cooperativity with colocalized partners, suggesting an underlying cis-regulatory syntax. To explore TF cooperativity in mammals, we analyze ∼500 mouse and human primary cells by combining an atlas of TF motifs, footprints, ChIP-seq, transcriptomes, and accessibility. We uncover two TF groups that colocalize with most expressed factors, forming stripes in hierarchical clustering maps. The first group includes lineage-determining factors that occupy DNA elements broadly, consistent with their key role in tissue-specific transcription. The second one, dubbed universal stripe factors (USFs), comprises ∼30 SP, KLF, EGR, and ZBTB family members that recognize overlapping GC-rich sequences in all tissues analyzed. Knockouts and single-molecule tracking reveal that USFs impart accessibility to colocalized partners and increase their residence time. Mammalian cells have thus evolved a TF superfamily with overlapping DNA binding that facilitate chromatin accessibility.
Keywords
Animals, Binding Sites, Chromatin, DNA, Humans, Mammals, Mice, Mice, Knockout, Protein Binding, Transcription Factors
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genomics Commons, Medical Sciences Commons, Oncology Commons
Comments
Supplementary Materials
PMID: 35863348