Identification of Heat Shock Factor 1 Molecular and Cellular Targets During Embryonic and Adult Female Meiosis

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2011 Jun 22

PMID 21690297

Citations 25

Authors

Florent Le Masson

Zak Razak

Mo Kaigo

Christophe Audouard

Colette Charry

Howard Cooke

J Timothy Westwood

Elisabeth S Christians

Affiliations

Soon will be listed here.

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.

Citing Articles

Genome-wide landscape of genetic diversity, runs of homozygosity, and runs of heterozygosity in five Alpine and Mediterranean goat breeds.

Pegolo S, Bisutti V, Mota L, Cecchinato A, Amalfitano N, Dettori M J Anim Sci Biotechnol. 2025; 16(1):33.

PMID: 40025542 PMC: 11874128. DOI: 10.1186/s40104-025-01155-3.

Non-cell-autonomous regulation of germline proteostasis by insulin/IGF-1 signaling-induced dietary peptide uptake via PEPT-1.

Muhammad T, Edwards S, Morphis A, Johnson M, de Oliveira V, Chamera T EMBO J. 2024; 43(21):4892-4921.

PMID: 39284915 PMC: 11535032. DOI: 10.1038/s44318-024-00234-x.

The stress response regulator HSF1 modulates natural killer cell anti-tumour immunity.

Hockemeyer K, Sakellaropoulos T, Chen X, Ivashkiv O, Sirenko M, Zhou H Nat Cell Biol. 2024; 26(10):1734-1744.

PMID: 39223375 DOI: 10.1038/s41556-024-01490-z.

Regulation of germline proteostasis by HSF1 and insulin/IGF-1 signaling.

Muhammad T, Li J Biochem Soc Trans. 2023; 51(2):501-512.

PMID: 36892215 PMC: 10355142. DOI: 10.1042/BST20220616.

HSF1 is a driver of leukemia stem cell self-renewal in acute myeloid leukemia.

Dong Q, Xiu Y, Wang Y, Hodgson C, Borcherding N, Jordan C Nat Commun. 2022; 13(1):6107.

PMID: 36245043 PMC: 9573868. DOI: 10.1038/s41467-022-33861-1.

References

Barbero J . Cohesins: chromatin architects in chromosome segregation, control of gene expression and much more. Cell Mol Life Sci. 2009; 66(13):2025-35. PMC: 11115881. DOI: 10.1007/s00018-009-0004-8. View

Hunt P, Hassold T . Sex matters in meiosis. Science. 2002; 296(5576):2181-3. DOI: 10.1126/science.1071907. View

Walpita D, LESPINASSE F, Desnuelle C, Ashley T, Paquis-Flucklinger V . MSH4 acts in conjunction with MLH1 during mammalian meiosis. FASEB J. 2000; 14(11):1539-47. DOI: 10.1096/fj.14.11.1539. View

Kan R, Sun X, Kolas N, Avdievich E, Kneitz B, Edelmann W . Comparative analysis of meiotic progression in female mice bearing mutations in genes of the DNA mismatch repair pathway. Biol Reprod. 2007; 78(3):462-71. DOI: 10.1095/biolreprod.107.065771. View

Vogt E, Kirsch-Volders M, Parry J, Eichenlaub-Ritter U . Spindle formation, chromosome segregation and the spindle checkpoint in mammalian oocytes and susceptibility to meiotic error. Mutat Res. 2007; 651(1-2):14-29. DOI: 10.1016/j.mrgentox.2007.10.015. View

Akerfelt M, Vihervaara A, Laiho A, Conter A, Christians E, Sistonen L . Heat shock transcription factor 1 localizes to sex chromatin during meiotic repression. J Biol Chem. 2010; 285(45):34469-76. PMC: 2966061. DOI: 10.1074/jbc.M110.157552. View

Zickler D . From early homologue recognition to synaptonemal complex formation. Chromosoma. 2006; 115(3):158-74. DOI: 10.1007/s00412-006-0048-6. View

Ghafari F, Gutierrez C, Hartshorne G . Apoptosis in mouse fetal and neonatal oocytes during meiotic prophase one. BMC Dev Biol. 2007; 7:87. PMC: 1965470. DOI: 10.1186/1471-213X-7-87. View

Gonsalves S, Moses A, Razak Z, Robert F, Westwood J . Whole-genome analysis reveals that active heat shock factor binding sites are mostly associated with non-heat shock genes in Drosophila melanogaster. PLoS One. 2011; 6(1):e15934. PMC: 3021535. DOI: 10.1371/journal.pone.0015934. View

10.

Hodges C, Hunt P . Simultaneous analysis of chromosomes and chromosome-associated proteins in mammalian oocytes and embryos. Chromosoma. 2002; 111(3):165-9. DOI: 10.1007/s00412-002-0195-3. View

11.

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

12.

Kallio M, Chang Y, Manuel M, Alastalo T, Rallu M, Gitton Y . Brain abnormalities, defective meiotic chromosome synapsis and female subfertility in HSF2 null mice. EMBO J. 2002; 21(11):2591-601. PMC: 125382. DOI: 10.1093/emboj/21.11.2591. View

13.

Yang F, Baumann C, De La Fuente R . Persistence of histone H2AX phosphorylation after meiotic chromosome synapsis and abnormal centromere cohesion in poly (ADP-ribose) polymerase (Parp-1) null oocytes. Dev Biol. 2009; 331(2):326-38. PMC: 2738933. DOI: 10.1016/j.ydbio.2009.05.550. View

14.

Revenkova E, Herrmann K, Adelfalk C, Jessberger R . Oocyte cohesin expression restricted to predictyate stages provides full fertility and prevents aneuploidy. Curr Biol. 2010; 20(17):1529-33. PMC: 2945217. DOI: 10.1016/j.cub.2010.08.024. View

15.

Peters A, Plug A, van Vugt M, de Boer P . A drying-down technique for the spreading of mammalian meiocytes from the male and female germline. Chromosome Res. 1997; 5(1):66-8. DOI: 10.1023/a:1018445520117. View

16.

Kwiatkowski N, Jelluma N, Filippakopoulos P, Soundararajan M, Manak M, Kwon M . Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function. Nat Chem Biol. 2010; 6(5):359-68. PMC: 2857554. DOI: 10.1038/nchembio.345. View

17.

Lenzi M, Smith J, Snowden T, Kim M, Fishel R, Poulos B . Extreme heterogeneity in the molecular events leading to the establishment of chiasmata during meiosis i in human oocytes. Am J Hum Genet. 2004; 76(1):112-27. PMC: 1196414. DOI: 10.1086/427268. View

18.

McMillan D, Christians E, Forster M, Xiao X, Connell P, Plumier J . Heat shock transcription factor 2 is not essential for embryonic development, fertility, or adult cognitive and psychomotor function in mice. Mol Cell Biol. 2002; 22(22):8005-14. PMC: 134743. DOI: 10.1128/MCB.22.22.8005-8014.2002. View

19.

De Felici M, Klinger F, Farini D, Scaldaferri M, Iona S, Lobascio M . Establishment of oocyte population in the fetal ovary: primordial germ cell proliferation and oocyte programmed cell death. Reprod Biomed Online. 2005; 10(2):182-91. DOI: 10.1016/s1472-6483(10)60939-x. View

20.

Chang Y, Ostling P, Akerfelt M, Trouillet D, Rallu M, Gitton Y . Role of heat-shock factor 2 in cerebral cortex formation and as a regulator of p35 expression. Genes Dev. 2006; 20(7):836-47. PMC: 1472286. DOI: 10.1101/gad.366906. View