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Publication : Identification of heat shock factor 1 molecular and cellular targets during embryonic and adult female meiosis.

First Author  Le Masson F Year  2011
Journal  Mol Cell Biol Volume  31
Issue  16 Pages  3410-23
PubMed ID  21690297 Mgi Jnum  J:175085
Mgi Id  MGI:5142351 Doi  10.1128/MCB.05237-11
Citation  Le Masson F, et al. (2011) Identification of Heat Shock Factor 1 Molecular and Cellular Targets during Embryonic and Adult Female Meiosis. Mol Cell Biol 31(16):3410-23
abstractText  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.
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