title: Identification of heat shock factor 1 molecular and cellular targets during embryonic and adult female meiosis.
abstract: Heat shock factor 1 (HSF1), while recognized as the major regulator of the heat shock transcriptional response, also exerts important functions during mammalian embryonic development and gametogenesis. In particular, HSF1 is required for oocyte maturation, the adult phase of meiosis preceding fertilization. To identify HSF1 target genes implicated in this process, comparative transcriptomic analyses were performed with wild-type and HSF-deficient oocytes. This revealed a network of meiotic genes involved in cohesin and synaptonemal complex (SC) structures, DNA recombination, and the spindle assembly checkpoint (SAC). All of them were found to be regulated by HSF1 not only during adult but also in embryonic phases of female meiosis. Additional investigations showed that SC, recombination nodules, and DNA repair were affected in Hsf1(-/-) oocytes during prenatal meiotic prophase I. However, targeting Hsf1 deletion to postnatal oocytes (using Zp3 Cre; Hsf1(loxP/loxP)) did not fully rescue the chromosomal anomalies identified during meiotic maturation, which possibly caused a persistent SAC activation. This would explain the metaphase I arrest previously described in HSF1-deficient oocytes since SAC inhibition circumvented this block. This work provides new insights into meiotic gene regulation and points out potential links between cellular stress and the meiotic anomalies frequently observed in humans.
authors.affiliation: Université Toulouse 3, UPS, UMR 5547, Centre de Biologie du Développement, 118 route de Narbonne (Bat 4R3B3), 31062 Toulouse Cedex 09, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Le Masson
authors.forename: Zak
authors.initials: Z
authors.lastname: Razak
authors.forename: Mo
authors.initials: M
authors.lastname: Kaigo
authors.forename: Christophe
authors.initials: C
authors.lastname: Audouard
authors.forename: Colette
authors.initials: C
authors.lastname: Charry
authors.forename: Howard
authors.initials: H
authors.lastname: Cooke
authors.forename: J Timothy
authors.initials: JT
authors.lastname: Westwood
authors.forename: Elisabeth S
authors.initials: ES
authors.lastname: Christians
mesh_terms: D000367:Age Factors; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D005718:Gametogenesis / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D053263:Gene Regulatory Networks; D000076249:Heat Shock Transcription Factors; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D014157:Transcription Factors