DNA methylation maintenance at heterochromatin.

DNA methylation at CpGs silences repetitive elements and transposable elements (TEs) within constitutive heterochromatin in the genome. Deregulation of DNA methylation at these sites and their subsequent derepression promotes genomic instability. Hypomethylation of constitutive heterochromatin is a molecular hallmark of aging and cancer, as well as the rare genetic disorder Immunodeficiency, Centromeric instability and Facial anomalies (ICF) syndrome. We here review our current understanding of the function and regulation of 5mC at heterochromatin, highlighting the ICF-related CDCA7-HELLS nucleosome remodeling complex as a key regulator of the heterochromatin environment.