Journal
EMBO JOURNAL
Volume 30, Issue 3, Pages 480-493Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2010.335
Keywords
Asf1b; breast cancer; histones; proliferation
Categories
Funding
- la Ligue Nationale contre le Cancer (Equipe labellisee Ligue)
- PIC Programs
- European Commission Network of Excellence Epigenome [LSHG-CT-2004-503433]
- European Commission ITN [FP7-PEOPLE-2007, FP7-PEOPLE-2008]
- ANR [ANR-09-BLAN-0257-01]
- INCa
- ERC [2009-AdG_20090506]
- University Pierre et Marie Curie (UPMC)
- Association pour la Recherche sur le Cancer (ARC)
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Mammalian cells possess two isoforms of the histone H3-H4 chaperone anti-silencing function 1 (Asf1), Asf1a and Asf1b. However to date, whether they have individual physiological roles has remained elusive. Here, we aim to elucidate the functional importance of Asf1 isoforms concerning both basic and applied aspects. First, we reveal a specific proliferation-dependent expression of human Asf1b unparalleled by Asf1a. Strikingly, in cultured cells, both mRNA and protein corresponding to Asf1b decrease upon cell cycle exit. Depletion of Asf1b severely compromises proliferation, leads to aberrant nuclear structures and a distinct transcriptional signature. Second, a major physiological implication is found in the applied context of tissue samples derived from early stage breast tumours in which we examined Asf1a/b levels. We reveal that overexpression of Asf1b mRNA correlate with clinical data and disease outcome. Together, our results highlight a distribution of tasks between the distinct Asf1 isoforms, which emphasizes a specialized function of Asf1b required for proliferation capacity. We discuss the implications of these results for breast cancer diagnosis and prognosis. The EMBO Journal (2011) 30, 480-493. doi:10.1038/emboj.2010.335; Published online 21 December 2010
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