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.
Original language | English (US) |
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Pages (from-to) | 3398-3411.e11 |
Journal | Molecular cell |
Volume | 82 |
Issue number | 18 |
DOIs | |
State | Published - Sep 15 2022 |
Externally published | Yes |
Keywords
- DNA motifs
- chromatin accessibility
- enhancer syntax
- gene expression
- mammalian genomes
- regulatory elements
- single molecule tracking
- transcription factors
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology