Keep Fingers on the CpG Islands

Xing Zhang, Robert M. Blumenthal, Xiaodong Cheng

Research output: Contribution to journalArticlepeer-review

Abstract

The post-genomic era has ushered in the extensive application of epigenetic editing tools, allowing for precise alterations of gene expression. The use of reprogrammable editors that carry transcriptional corepressors has significant potential for long-term epigenetic silencing for the treatment of human diseases. The ideal scenario involves precise targeting of a specific genomic location by a DNA-binding domain, ensuring there are no off-target effects and that the process yields no genetic remnants aside from specific epigenetic modifications (i.e., DNA methylation). A notable example is a recent study on the mouse Pcsk9 gene, crucial for cholesterol regulation and expressed in hepatocytes, which identified synthetic zinc-finger (ZF) proteins as the most effective DNA-binding editors for silencing Pcsk9 efficiently, specifically, and persistently. This discussion focuses on enhancing the specificity of ZF-array DNA binding by optimizing interactions between specific amino acids and DNA bases across three promoters containing CpG islands.

Original languageEnglish (US)
Article number23
JournalEpigenomes
Volume8
Issue number2
DOIs
StatePublished - Jun 2024

Keywords

  • C2H2 zinc-finger arrays
  • CpG islands in promoters
  • CpG-free segments
  • DNA methylation
  • DNA sequence-specific binding
  • epigenetic reprogramming

ASJC Scopus subject areas

  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Genetics
  • Health, Toxicology and Mutagenesis

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