Specific Methyl-CpG Configurations Define Cell Identity through Gene Expression Regulation

Int J Mol Sci. 2023 Jun 9;24(12):9951. doi: 10.3390/ijms24129951.

Abstract

Cell identity is determined by the chromatin structure and profiles of gene expression, which are dependent on chromatin accessibility and DNA methylation of the regions critical for gene expression, such as enhancers and promoters. These epigenetic modifications are required for mammalian development and are essential for the establishment and maintenance of the cellular identity. DNA methylation was once thought to be a permanent repressive epigenetic mark, but systematic analyses in various genomic contexts have revealed a more dynamic regulation than previously thought. In fact, both active DNA methylation and demethylation occur during cell fate commitment and terminal differentiation. To link methylation signatures of specific genes to their expression profiles, we determined the methyl-CpG configurations of the promoters of five genes switched on and off during murine postnatal brain differentiation by bisulfite-targeted sequencing. Here, we report the structure of significant, dynamic, and stable methyl-CpG profiles associated with silencing or activation of the expression of genes during neural stem cell and brain postnatal differentiation. Strikingly, these methylation cores mark different mouse brain areas and cell types derived from the same areas during differentiation.

Keywords: DNA methylation; cell identity; gene expression; methyl-CpG.

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Chromatin / genetics
  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic
  • Gene Expression Regulation*
  • Mammals / genetics
  • Mice

Substances

  • Chromatin

Grants and funding

This work was supported by #NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006)—A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022). A. Pezone is supported by the Italian Ministry of University and Scientific Research (P.R.I.N. 2017237P5x).