Expression of the repeat genome and aberrant epigenetic factors in cancer

摘要

Nearly half of the human genome consists of noncodingrepetitive DNA elements, including tandem satelliterepeats in large blocks at the pericentric regions of chromosomesand intergenic repetitive elements. While bothrepeat types were long thought to remain mostly silent,recent evidence indicates that repeats can be expressed,but the extent and regulation of their expression or theirpotential function(s) remain to be elucidated. Due to theircritical location within regions vital for cell division, it isexpected that tight regulation of pericentric satellitesequences is essential for both epigenetic and genetic stability.Our data suggests aberrant expression of pericentricsatellite RNA is tightly linked to epigenetic misregulationin cancer. It is well known that epigenetic changes can beimportant in cancer initiation and progression, but studieshave focused primarily on the inappropriate silencing andmethylation of tumor suppressor genes. While pathologistshave long noted the loss of heterochromatic organizationin cancer nuclei, and hypomethylation of satelliteDNA has been observed, the misregulation of repeatRNAs has only recently been described. Our results providea link between overexpression of repeat RNAs andaberrant distribution of epigenetic factors in cancer. Ourdata suggests regulation of the repeat genome has potentiallyimportant roles in both normal and neoplastic cellsin their ability to affect distribution and recruitment ofepigenetic factors.