DAXX maintains chromosomal stability by keeping methylation levels at specific repetitive elements

Chromosomal instability (CIN), a common hallmark in most solid cancers, is characterized by structural and numerical errors during cell division. Maintenance and repression of constitutive heterochromatin, including regions like telomeres and pericentromeres, as well as repetitive elements (RE), is a critical step in preventing CIN. The histone chaperone DAXX, together with other epigenetic factors, helps preserve repression at these loci by depositing histone H3.3 and supporting histone repressive marks and DNA methylation. In the present study, we knocked down DAXX in the CIN-stable colorectal cancer cell line HCT116. We observed an increase in micronuclei and loss of DNA methylation at specific heterochromatic regions, which in turn led to the abnormal expression of repetitive elements such as the LRT7Y subfamily, normally active only during development. These findings highlight the role of DAXX in maintaining genomic stability by regulating heterochromatin and silencing specific repetitive elements.