Regulatory mechanism and biological function of UHRF1-DNMT1-mediated DNA methylation

Funct Integr Genomics. 2022 Dec;22(6):1113-1126. doi: 10.1007/s10142-022-00918-9. Epub 2022 Nov 14.

Abstract

The maintenance of epigenetic characteristics is essential for the normal growth and development of organisms. The maintenance of DNA methylation is an important way to maintain the epigenetic characteristics of organisms. DNMT1 is a core enzyme that maintains intracellular DNA methylation, and UHRF1, as a cofactor of DNMT1, plays an important role in the regulation of DNA methylation by DNMT1. The maintenance of DNA methylation mediated by UHRF1-DNMT1 complex is involved in the regulation of many vital activities. This review describes the whole molecular process of UHRF1-DNMT1 pathway from the opening of inhibitory structure to the end of maintenance methylation in detail and lists some latest biological research progress related to this pathway in the development of early embryonic, maintenance of pluripotency of embryonic stem cells, regulation of expression of imprinted genes, inactivation of X chromosome, and development of cancer. Finally, put forward some problems remained to be solved at present and new thoughts.

Keywords: DNA methylation; DNMT1; Embryonic stem cells; UHRF1.

Publication types

  • Review

MeSH terms

  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • DNA (Cytosine-5-)-Methyltransferases* / genetics
  • DNA (Cytosine-5-)-Methyltransferases* / metabolism
  • DNA Methylation*
  • Protein Processing, Post-Translational
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • DNA (Cytosine-5-)-Methyltransferases
  • CCAAT-Enhancer-Binding Proteins
  • Ubiquitin-Protein Ligases