Pericentromeric Satellites: Implications For Chromosome Evolution And Misregulation In Disease

Abstract

Nearly half of the human genome consists of noncoding repetitive DNA elements, including tandem satellite repeats in large blocks at the pericentromeric regions of chromosomes and intergenic repetitive elements. While both repeat 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 their potential function(s) remain to be elucidated. The location of satellite sequences within pericentromeric regions is largely conserved; this is in contrast to the apparent lack of sequence conservation among even closely related species. Due to their critical location within regions vital for cell division, it is expected that tight regulation of pericentromeric satellite sequences is essential for both epigenetic and genetic stability. We have developed tools to examine the effect of pericentromeric satellite expression on cell division and the distribution of key regulatory proteins. Our data suggests induced expression of pericentromeric satellite RNA is tightly linked to both epigenetic instability and aberrant cell division. Further, using a comparative genomics approach, we examine the evolutionary conservation of a subset of satellite sequences found to be particularly prone to misregulation in cancer