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Review
. 2024 May:225:20-27.
doi: 10.1016/j.ymeth.2024.03.001. Epub 2024 Mar 11.

Using synthetic genome readers/regulators to interrogate chromatin processes: A brief review

Steven J Philips  1 , Adithi Danda  1 , Aseem Z Ansari  2
Affiliations
Review

Using synthetic genome readers/regulators to interrogate chromatin processes: A brief review

Steven J Philips et al. Methods. 2024 May.

Abstract

Aberrant gene expression underlies numerous human ailments. Hence, developing small molecules to target and remedy dysfunctional gene regulation has been a long-standing goal at the interface of chemistry and medicine. A major challenge for designing small molecule therapeutics aimed at targeting desired genomic loci is the minimization of widescale disruption of genomic functions. To address this challenge, we rationally design polyamide-based multi-functional molecules, i.e., Synthetic Genome Readers/Regulators (SynGRs), which, by design, target distinct sequences in the genome. Herein, we briefly review how SynGRs access chromatin-bound and chromatin-free genomic sites, then highlight the methods for the study of chromatin processes using SynGRs on positioned nucleosomes in vitro or disease-causing repressive genomic loci in vivo.

Keywords: COSMIC; CSI; DiSEL; Genome-targeting; Nucleosome; Polyamide; SEL; SynGR; Synthetic transcription factors; Transcription.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AZA: founder of Vista Motif LLC, Winstep Forward non-profit 501(C) (3) and co-founder of Design Therapeutics. SJP and AD: none.

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