Faculty, Staff and Student 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
DOI
10.1016/j.molcel.2022.06.029
PMID
35863348
PMCID
PMC9481673
PubMedCentral® Posted Date
September 2023
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genomics Commons, Medical Sciences Commons, Oncology Commons
Comments
Supplementary Materials
PMID: 35863348