Heterochromatin protein 1alpha: a hallmark of cell proliferation relevant to clinical oncology.
Mammalian cells contain three closely related heterochromatin protein 1 (HP1) isoforms, HP1alpha, beta and gamma, 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 HP1alpha shows a proliferation-dependent regulation, which neither HP1beta nor gamma display. During transient cell cycle exit, the HP1alpha mRNA and protein levels diminish. Transient depletion of HP1alpha, but not HP1beta or gamma, 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 HP1alpha mRNA and protein, which correlates with clinical data and disease outcome. Our results unveil a specific expression pattern for the HP1alpha isoform, suggesting a unique function related to cell division and tumour growth. The overexpression of HP1alpha constitutes a new example of a potential epigenetic contribution to tumourigenesis that is of clinical interest for cancer prognosis.
De Koning
Leanne
L
Laboratory of Nuclear Dynamics and Genome Plasticity (UMR218), Institut Curie/CNRS/UPMC, 26 Rue d'Ulm, 75248 Paris Cedex 05, France.
Savignoni
Alexia
A
Boumendil
Charlène
C
Rehman
Haniya
H
Asselain
Bernard
B
Sastre-Garau
Xavier
X
Almouzni
Geneviève
G
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
C000715593:CBX1 protein, human; C000715594:CBX5 protein, human; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D012333:RNA, Messenger; D000090266:Chromobox Protein Homolog 5