ArticleProceedings of the National Academy of Sciences of the United States of America2016
Synthetic genome readers target clustered binding sites across diverse chromatin states.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Positional isomers of Indolyl-benzodiazepines display dissimilar binding and recruitment of BET transcriptional regulators to targeted genomic loci.Bioorganic chemistry · 2025Article
- A "Goldilocks Zone" for Recruiting BET Proteins with Bromodomain-1-Selective Ligands.ACS chemical biology · 2024Article
- Using synthetic genome readers/regulators to interrogate chromatin processes: A brief review.Methods (San Diego, Calif.) · 2024Review
- Domain-Selective BET Ligands Yield Next-Generation Synthetic Genome Readers/Regulators with Nonidentical Cellular Functions.Journal of the American Chemical Society · 2023Article
- Chem-map profiles drug binding to chromatin in cells.Nature biotechnology · 2023Article
- Getting a handle on chemical probes of chomatin readers.Future medicinal chemistry · 2021Article
- Single position substitution of hairpin pyrrole-imidazole polyamides imparts distinct DNA-binding profiles across the human genome.PloS one · 2020Article
- Sequence specific suppression of androgen receptor-DNA binding in vivo by a Py-Im polyamide.Nucleic acids research · 2019Article
- Structural and Kinetic Profiling of Allosteric Modulation of Duplex DNA Induced by DNA-Binding Polyamide Analogues.Chemistry (Weinheim an der Bergstrasse, Germany) · 2019Article
- Specificity landscapes unmask submaximal binding site preferences of transcription factors.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides.Nucleic acids research · 2018Article
- Synthetic transcription elongation factors license transcription across repressive chromatin.Science (New York, N.Y.) · 2017Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Targeting the genome with sequence-specific DNA-binding molecules is a major goal at the interface of chemistry, biology, and precision medicine. Polyamides, composed of N-methylpyrrole and N-methylimidazole monomers, are a class of synthetic molecules that can be rationally designed to "read" specific DNA sequences. However, the impact of different chromatin states on polyamide binding in live cells remains an unresolved question that impedes their deployment in vivo. Here, we use cross-linking of small molecules to isolate chromatin coupled to sequencing to map the binding of two bioactive and structurally distinct polyamides to genomes directly within live H1 human embryonic stem cells. This genome-wide view from live cells reveals that polyamide-based synthetic genome readers bind cognate sites that span a range of binding affinities. Polyamides can access cognate sites within repressive heterochromatin. The occupancy patterns suggest that polyamides could be harnessed to target loci within regions of the genome that are inaccessible to other DNA-targeting molecules.
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