Mammalian Heat Shock Factor 1 Is Essential for Oocyte Meiosis and Directly Regulates Hsp90α Expression

doi:10.1074/jbc.M808819200

Mammalian Heat Shock Factor 1 Is Essential for Oocyte Meiosis and Directly Regulates Hsp90α Expression^*

^{^‡}UPS, Centre de Biologie du Développement-UMR5547, 4R3B3, Université de Toulouse, 118 route de Narbonne, F-31062 Toulouse, France, ^{^§}Department of Biology, Åbo Akademi University, Turku Centre for Biotechnology, University of Turku, Åbo Akademi University, 20520 Turku, Finland, and ^{^¶}Département de Biologie, Université de Mons-Hainaut, Facultéde Médecine-Pharmacie, 7000 Mons, Belgium

2 To whom correspondence should be addressed. Fax: 33-561-55-6507; E-mail: Elisabeth.Christians{at}cict.fr.

Abstract

Heat shock transcription factor 1 (HSF1) is the main regulator of the stress response that triggers the transcription of several genes encoding heat shock proteins (Hsps). Hsps act as molecular chaperones involved in protein folding, stability, and trafficking. HSF1 is highly expressed in oocytes and Hsf1 knock-out in mice revealed that in the absence of stress this factor plays an important role in female reproduction. We previously reported that Hsf1^-/- females produce oocytes but no viable embryos. Consequently, we asked whether oocytes require HSF1 to regulate a particular set of Hsps necessary for them to develop. We find that Hsp90α (Hspaa1) is the major HSF1-dependent chaperone inasmuch as Hsf1 knock-out resulted in Hsp90-depleted oocytes. These oocytes exhibited delayed germinal vesicle breakdown (or G₂/M transition), partial meiosis I block, and defective asymmetrical division. To probe the role of Hsp90α in this meiotic syndrome, we analyzed meiotic maturation in wild-type oocytes treated with a specific inhibitor of Hsp90, 17-allylamino-17-demethoxy-geldanamycin, and observed similar defects. At the molecular level we showed that, together with these developmental anomalies, CDK1 and MAPK, key meiotic kinases, were significantly disturbed. Thus, our data demonstrate that HSF1 is a maternal transcription factor essential for normal progression of meiosis.

Footnotes

↵³ The abbreviations used are: HSF, heat shock factor; Hsp, heat shock protein; ChIP, chromatin immunoprecipitation; MII, metaphase II; GVBD, germinal vesicle (GV) breakdown; 17AAG, 17-(allylamino)-17-demethoxygelda-namycin; MEK, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase; IBMX, isobutylmethylxanthine; ERK, extracellular signal-regulated kinase; MAPK, mitogen-activated protein (MAP) kinase; ERK1/2-P, ERK1/2 phosphorylated forms; qPCR, quantitative PCR.
↵^* This work was funded by the Centre National de la Recherche Scientifique, le Ministère de l'Education Nationale et de la Recherche, la Fondation pour la Recherche Médicale (to E. S. C.), l'Association pour la Recherche contre le Cancer (to A. M.), travel grants funding from the University Toulouse III (UPS) (to A. M. and E. S. C.), and by The Academy of Finland, The Sigrid Jusélius Foundation, and Åbo Akademi University (to L. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵ The on-line version of this article (available at http://www.jbc.org) contains supplemental Tables S1-S3 and Figs. 1 and 2.
↵¹ Supported by the Turku Graduate School of Biochemical Sciences.
- Received November 20, 2008.
- Revision received January 20, 2009.
The American Society for Biochemistry and Molecular Biology, Inc.