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

Publisher: Academic Press Country of Publication: United States NLM ID: 9426302 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9130 (Electronic) Linking ISSN: 10462023 NLM ISO Abbreviation: Methods Subsets: MEDLINE

Publication: Duluth, MN : Academic Press
Original Publication: San Diego : Academic Press, c1990-

Chromatin*/genetics ; Chromatin*/metabolism ; Nucleosomes*/genetics ; Nucleosomes*/metabolism; Humans ; Nylons/chemistry ; Nylons/pharmacology ; Gene Expression Regulation/drug effects ; Animals ; Chromatin Assembly and Disassembly/drug effects ; Chromatin Assembly and Disassembly/genetics ; Genomics/methods

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.
Competing Interests: 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.
(Copyright © 2024 Elsevier Inc. All rights reserved.)

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R01 NS108376 United States NS NINDS NIH HHS

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

0 (Chromatin)
0 (Nucleosomes)
0 (Nylons)

Date Created: 20240312 Date Completed: 20240426 Latest Revision: 20240429

20240429

PMC11055675

10.1016/j.ymeth.2024.03.001

38471600