1. 'Stripe' transcription factors provide accessibility to co-binding partners in mammalian genomes
- Author
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Yongbing Zhao, Supriya V. Vartak, Andrea Conte, Xiang Wang, David A. Garcia, Evan Stevens, Seol Kyoung Jung, Kyong-Rim Kieffer-Kwon, Laura Vian, Timothy Stodola, Francisco Moris, Laura Chopp, Silvia Preite, Pamela L. Schwartzberg, Joseph M. Kulinski, Ana Olivera, Christelle Harly, Avinash Bhandoola, Elisabeth F. Heuston, David M. Bodine, Raul Urrutia, Arpita Upadhyaya, Matthew T. Weirauch, Gordon Hager, Rafael Casellas, 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., and Casellas, R.
- Subjects
Mammals ,Mice, Knockout ,Binding Sites ,Animal ,Binding Site ,single molecule tracking ,Cell Biology ,DNA ,Mammal ,Chromatin ,Mice ,chromatin accessibility ,gene expression ,Animals ,Humans ,enhancer syntax ,DNA motif ,mammalian genome ,Molecular Biology ,transcription factor ,regulatory element ,Human ,Protein Binding ,Transcription Factors - 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.
- Published
- 2021