# Interconnected Codons: Unravelling the Epigenetic Significance of Flanking Sequences in CpG Dyads

## TL;DR

This paper explores how pairs of codons containing CpG sequences influence gene function and regulation, especially during embryonic development.

## Contribution

The study reveals a novel connection between CpG codon dyads and gene function, linking them to specific biological processes and developmental stages.

## Key findings

- High CpG codon dyad density is associated with homeobox domains and RNA polymerase II transcription factors.
- Low CpG codon dyad density is linked to DNA damage repair and mitosis.
- CpG-containing genes are more expressed during embryonic development, suggesting a role in gene regulation.

## Abstract

Hypothesizing that CpG codon dyads, formed by consecutive codons containing a cytosine-guanine pair (NNC-GNN), may play a crucial role in gene function, we conducted an extensive analysis to investigate their distribution and conservation within mammalian genes. Our findings reveal that genes characterized by a high density of CpG codon dyads are notably associated with homeobox domains and RNA polymerase II transcription factors. Conversely, genes exhibiting low CpG codon dyad density have links to DNA damage repair and mitosis. Importantly, our study identifies a re-markable increase in expressed genes that harbor CpG during embryonic development, suggesting their potential involvement in gene regulation at these developmental stages. These results under-score the functional significance of CpG codon dyads in DNA methylation and gene expression, fur-ther demonstrating the coevolution of consecutive codons and their contribution to codon usage bias.

The online version contains supplementary material available at 10.1007/s00239-024-10172-1.