The chapter discusses the role of DNA methylation in epigenetic memory and gene regulation during mammalian development. DNA methylation patterns are highly variable across different species, with vertebrates having the highest levels of methylation. The maintenance of methylation patterns is crucial for heritability, but it is not perfect, leading to dynamic changes in methylation levels over time and between cell generations. CpG islands, which are unmethylated regions near gene promoters, are particularly stable and often associated with tissue-specific gene expression. De novo methylation, initiated by de novo methyltransferases DNMT3A and DNMT3B, occurs in early embryonic cells and can affect genes that are already silent. The mechanisms behind de novo methylation include targeting to specific DNA sequences and the influence of chromatin structure. DNA methylation contributes to the stable silencing of genes, such as those involved in X chromosome inactivation and genomic imprinting. However, loss of methylation can lead to gene activation, as seen in studies using DNA methylation inhibitors and knockout mice. The chapter also explores the potential role of RNA-directed DNA methylation and the involvement of histone modifications in the regulation of DNA methylation. Overall, DNA methylation is a complex process that plays a critical role in maintaining cellular memory and gene regulation during development.The chapter discusses the role of DNA methylation in epigenetic memory and gene regulation during mammalian development. DNA methylation patterns are highly variable across different species, with vertebrates having the highest levels of methylation. The maintenance of methylation patterns is crucial for heritability, but it is not perfect, leading to dynamic changes in methylation levels over time and between cell generations. CpG islands, which are unmethylated regions near gene promoters, are particularly stable and often associated with tissue-specific gene expression. De novo methylation, initiated by de novo methyltransferases DNMT3A and DNMT3B, occurs in early embryonic cells and can affect genes that are already silent. The mechanisms behind de novo methylation include targeting to specific DNA sequences and the influence of chromatin structure. DNA methylation contributes to the stable silencing of genes, such as those involved in X chromosome inactivation and genomic imprinting. However, loss of methylation can lead to gene activation, as seen in studies using DNA methylation inhibitors and knockout mice. The chapter also explores the potential role of RNA-directed DNA methylation and the involvement of histone modifications in the regulation of DNA methylation. Overall, DNA methylation is a complex process that plays a critical role in maintaining cellular memory and gene regulation during development.