Heterochromatin protein lα: a hallmark of cell proliferation relevant to clinical oncology

Abstract

Mammalian cells contain three closely related heterochromatin protein 1 (HPi) isoforms, HPia, b and g, which, by analogy to their unique counterpart in Schizosaccharomyces pombe, have been implicated in gene silencing, genome stability and chromosome segregation. However, the individual importance of each isoform during normal cell cycle and disease has remained an unresolved issue. Here, we reveal that HP1a shows a proliferation-dependent regulation, which neither HPib nor g display. During transient cell cycle exit, the HPia mRNA and protein levels diminish. Transient depletion of HPia, but not HPib or g,in tumoural and primary human cells leads to defects in chromosome segregation. Notably, analysis of an annotated collection of samples derived from carcinomas reveals an overexpression of HPia mRNA and protein, which correlates with clinical data and disease outcome. Our results unveil a specific expression pattern for the HPia isoform, suggesting a unique function related to cell division and tumour growth. The overexpression of HPia constitutes a new example of a potential epigenetic contribution to tumourigenesis that is of clinical interest for cancer prognosis. © 2009 EMBO Molecular Medicine.