ArticlePLoS computational biology2024
Transcription factor interactions explain the context-dependent activity of CRX binding sites.
Article in PLoS computational biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Enhanced chromatin compaction is associated with de novo expression of a nuclear microprotein, global loss of H3 acetylation and local transcriptional changes in retinal rod photoreceptors.Research square · 2026Article
- Stress Responsive bZIP Transcription Factors ATF4 and BACH1 Cooperate With MAF-Family bZIP Protein NRL to Fine-Tune Rod Photoreceptor Gene Expression.Investigative ophthalmology & visual science · 2026Article
- Bifunctional transcriptional effector domains control gene expression pulses in an occupancy-dependent manner.bioRxiv : the preprint server for biology · 2025Article
- Active learning of enhancers and silencers in the developing neural retina.Cell systems · 2025Article
- The emergence and evolution of gene expression in genome regions replete with regulatory motifs.eLife · 2024Article
- Molecular basis of CRX/DNA recognition and stoichiometry at the Ret4 response element.Structure (London, England : 1993) · 2024Article
- Pathogenic variants inGenome research · 2024Article
- Pathogenic variants in Crx have distinct cis-regulatory effects on enhancers and silencers in photoreceptors.bioRxiv : the preprint server for biology · 2023Article
- Active learning of enhancer and silencer regulatory grammar in photoreceptors.bioRxiv : the preprint server for biology · 2023Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The effects of transcription factor binding sites (TFBSs) on the activity of a cis-regulatory element (CRE) depend on the local sequence context. In rod photoreceptors, binding sites for the transcription factor (TF) Cone-rod homeobox (CRX) occur in both enhancers and silencers, but the sequence context that determines whether CRX binding sites contribute to activation or repression of transcription is not understood. To investigate the context-dependent activity of CRX sites, we fit neural network-based models to the activities of synthetic CREs composed of photoreceptor TFBSs. The models revealed that CRX binding sites consistently make positive, independent contributions to CRE activity, while negative homotypic interactions between sites cause CREs composed of multiple CRX sites to function as silencers. The effects of negative homotypic interactions can be overcome by the presence of other TFBSs that either interact cooperatively with CRX sites or make independent positive contributions to activity. The context-dependent activity of CRX sites is thus determined by the balance between positive heterotypic interactions, independent contributions of TFBSs, and negative homotypic interactions. Our findings explain observed patterns of activity among genomic CRX-bound enhancers and silencers, and suggest that enhancers may require diverse TFBSs to overcome negative homotypic interactions between TFBSs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.