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.
“Stripe” transcription factors provide accessibility to co-binding partners in mammalian genomes / Zhao, Y.; Vartak, S. V.; Conte, A.; Wang, X.; Garcia, D. A.; Stevens, E.; Kyoung Jung, S.; Kieffer-Kwon, K. -R.; Vian, L.; Stodola, T.; Moris, F.; Chopp, L.; Preite, S.; Schwartzberg, P. L.; Kulinski, J. M.; Olivera, A.; Harly, C.; Bhandoola, A.; Heuston, E. F.; Bodine, D. M.; Urrutia, R.; Upadhyaya, A.; Weirauch, M. T.; Hager, G.; Casellas, R.. - In: MOLECULAR CELL. - ISSN 1097-2765. - 82:18(2022). [10.1016/j.molcel.2022.06.029]
“Stripe” transcription factors provide accessibility to co-binding partners in mammalian genomes
Conte A.Co-primo
;
2022
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
