title: Asf1b, the necessary Asf1 isoform for proliferation, is predictive of outcome in breast cancer.
abstract: 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.
authors.affiliation: Institut Curie, UMR218, Nuclear Dynamics and Genome Plasticity, Paris, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Corpet
authors.forename: Leanne
authors.initials: L
authors.lastname: De Koning
authors.forename: Joern
authors.initials: J
authors.lastname: Toedling
authors.forename: Alexia
authors.initials: A
authors.lastname: Savignoni
authors.forename: Frédérique
authors.initials: F
authors.lastname: Berger
authors.forename: Charlène
authors.initials: C
authors.lastname: Lemaître
authors.forename: Roderick J
authors.initials: RJ
authors.lastname: O'Sullivan
authors.forename: Jan
authors.initials: J
authors.lastname: Karlseder
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Barillot
authors.forename: Bernard
authors.initials: B
authors.lastname: Asselain
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.forename: Geneviève
authors.initials: G
authors.lastname: Almouzni
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008856:Microscopy, Fluorescence; D018832:Molecular Chaperones / Q000378:metabolism*; D011237:Predictive Value of Tests; D020033:Protein Isoforms / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C491640:ASF1B protein, human; D018797:Cell Cycle Proteins; D018832:Molecular Chaperones; D020033:Protein Isoforms; D034741:RNA, Small Interfering