Ayte’s Lab

Lab Members

José Ayté, PI
Alberto González-Medina, PhD student
Esther Pazo, PhD student
Sonia Borao, PhD student
Mercè Carmona, Technician

Track record of the group

Meiosis is the only exception to a regular cell cycle since there are two nuclear divisions (meiosis I and meiosis II) without an intervening DNA synthesis.  My laboratory is interested in characterizing the molecular bases that control the different gene expression programs in the fission yeast Schizosacharomyces pombe during meiosis.

Regarding transcription, we have shown which are the main players controlling the transcription of the genes required for S phase, focusing on the regulation of the MBF complex.  We have determined which the repressors of this transcription factor are and when these repressors are inactivated (Gomez-Escoda et al, 2011; Ivanova et al, 2011; Ivanova et al, 2013).

On top of the regulation of transcription, S. pombe cells require a meiotic-specific splicing program.  This splicing program ensures that fission yeast cells can express proteins that are only required during meiosis and that they are not present during the mitotic cycle; other mechanisms have been described to avoid unwanted expression of meiotic genes during mitotic cycle (Moldon et al, 2009). Among the genes with regulated splicing, we have described the cyclin Rem1 (Malapeira et al, 2007; Moldon et al, 2008).  We have recently shown that part of this splicing program depends on two proteins of the Forkhead family, Fkh2 and Mei4 (Alves-Rodrigues et al, 2016).

Finally, we have set up a system that allows the chemical induction of synchronous meiosis (Guerra-Moreno et al, 2012).  The great advantage of this new system is that it can be combined with all the temperature-sensitive alleles of splicing factors, which allows the individual determination of the role of each factor in the meiotic splicing program.

Most relevant publications

  1. A meiosis-specific cyclin regulated by splicing is required for proper progression through meiosis. Malapeira J, Moldón A, Hidalgo E, Smith GR, Nurse P, Ayté J. Mol Cell Biol. 2005 Aug;25(15):6330-7.
  2. Promoter-driven splicing regulation in fission yeast. Moldón A, Malapeira J, Gabrielli N, Gogol M, Gómez-Escoda B, Ivanova T, Seidel C, Ayté J. Nature. 2008 Oct 16;455(7215):997-1000. doi: 10.1038/nature07325. Epub 2008 Sep 24.
  3. At the (3′) end, you’ll turn to meiosis. Moldón A, Ayté J.  Nat Struct Mol Biol. 2009 Apr;16(4):350-1. doi: 10.1038/nsmb0409-350.
  4. Yox1 links MBF-dependent transcription to completion of DNA synthesis. Gómez-Escoda B, Ivanova T, Calvo IA, Alves-Rodrigues I, Hidalgo E, Ayté J.  EMBO Rep. 2011 Jan;12(1):84-9. doi: 10.1038/embor.2010.187. Epub 2010 Dec 3.
  5. G1/S transcription and the DNA synthesis checkpoint: common regulatory mechanisms. Ivanova T, Gómez-Escoda B, Hidalgo E, Ayté J.  Cell Cycle. 2011 Mar 15;10(6):912-5. Epub 2011 Mar 15.
  6. Chemical genetic induction of meiosis in Schizosaccharomyces pombe. Guerra-Moreno A, Alves-Rodrigues I, Hidalgo E, Ayté J.  Cell Cycle. 2012 Apr 15;11(8):1621-5. doi: 10.4161/cc.20051. Epub 2012 Apr 15.
  7. The DNA damage and the DNA replication checkpoints converge at the MBF transcription factor. Ivanova T, Alves-Rodrigues I, Gómez-Escoda B, Dutta C, DeCaprio JA, Rhind N, Hidalgo E, Ayté J.  Mol Biol Cell. 2013 Nov;24(21):3350-7. doi: 10.1091/mbc.E13-05-0257. Epub 2013 Sep 4.
  8. Binding of the transcription factor Atf1 to promoters serves as a barrier to phase nucleosome arrays and avoid cryptic transcription. García P, Paulo E, Gao J, Wahls WP, Ayté J, Lowy E, Hidalgo E.  Nucleic Acids Res. 2014;42(16):10351-9. doi: 10.1093/nar/gku704. Epub 2014 Aug 13.
  9. A genetic approach to study H2O2 scavenging in fission yeast–distinct roles of peroxiredoxin and catalase. Paulo E, García-Santamarina S, Calvo IA, Carmona M, Boronat S, Domènech A, Ayté J, Hidalgo E.  Mol Microbiol. 2014 Apr;92(2):246-57. doi: 10.1111/mmi.12548. Epub 2014 Mar 6.
  10. Monitoring in vivo reversible cysteine oxidation in proteins using ICAT and mass spectrometry. García-Santamarina S, Boronat S, Domènech A, Ayté J, Molina H, Hidalgo E.  Nat Protoc. 2014 May;9(5):1131-45. doi: 10.1038/nprot.2014.065. Epub 2014 Apr 17.
  11. A cascade of iron-containing proteins governs the genetic iron starvation response to promote iron uptake and inhibit iron storage in fission yeast. Encinar del Dedo J, Gabrielli N, Carmona M, Ayté J, Hidalgo E.  PLoS Genet. 2015 Mar 25;11(3):e1005106. doi: 10.1371/journal.pgen.1005106. eCollection 2015 Mar.
  12. A functional genome-wide genetic screening identifies new pathways controlling the G1/S transcriptional wave. Gaspa L, González-Medina A, Hidalgo E, Ayté J.  Cell Cycle. 2016;15(5):720-9. doi: 10.1080/15384101.2016.1148839.
  13. Prp4 Kinase Grants the License to Splice: Control of Weak Splice Sites during Spliceosome Activation. Eckert D, Andrée N, Razanau A, Zock-Emmenthal S, Lützelberger M, Plath S, Schmidt H, Guerra-Moreno A, Cozzuto L, Ayté J*, Käufer NF*.  PLoS Genet. 2016 Jan 5;12(1):e1005768. doi: 10.1371/journal.pgen.1005768. eCollection 2016 Jan. *Co-corresponding authors
  1. Genome-wide Screening of Regulators of Catalase Expression: Role of a Transcription Complex and Histone and tRNA Modification Complexes on Adaptation to Stress. García P, Encinar Del Dedo J, Ayté J*, Hidalgo E*.  J Biol Chem. 2016 Jan 8;291(2):790-9. doi: 10.1074/jbc.M115.696658. Epub 2015 Nov 13.*Co-corresponding authors
  1. Spatiotemporal Control of Forkhead Binding to DNA Regulates the Meiotic Gene Expression Program. Alves-Rodrigues I, Ferreira PG, Moldón A, Vivancos AP, Hidalgo E, Guigó R, Ayté J.  Cell Rep. 2016 Feb 2;14(4):885-895. doi: 10.1016/j.celrep.2015.12.074. Epub 2016 Jan 21.
  2. Lack of a peroxiredoxin suppresses the lethality of cells devoid of electron donors by channelling electrons to oxidized ribonucleotide reductase. Boronat S, Domènech A, Carmona M, García-Santamarina S, Bañó MC, Ayté J*, Hidalgo E*.  PLoS Genet. 2017 Jun 22;13(6):e1006858. doi: 10.1371/journal.pgen.1006858. eCollection 2017 Jun.*Co-corresponding authors
  1. Deciphering the role of the signal- and Sty1 kinase-dependent phosphorylation of the stress-responsive transcription factor Atf1 on gene activation. Salat-Canela C, Paulo E, Sánchez-Mir L, Carmona M, Ayté J, Oliva B, Hidalgo E. J Biol Chem. 2017 Aug 18;292(33):13635-13644. doi: 10.1074/jbc.M117.794339. Epub 2017 Jun 26.
  2. Phospho-mimicking Atf1 mutants bypass the transcription activating function of the MAP kinase Sty1 of fission yeast. Sánchez-Mir L, Salat-Canela C, Paulo E, Carmona M, Ayté J, Oliva B, Hidalgo E.  Curr Genet. 2017 Aug 10. doi: 10.1007/s00294-017-0730-7. [Epub ahead of print] Review.

Ayte

Aim of the research work

We want to characterize now the early transcriptional wave, which includes genes required for pre-meiotic S phase and genes required for recombination. We know that the expression of both set of genes are dependent on the MBF complex (like for the mitotic S phase), but during meiosis is redirected to a broader set of genes since many are not transcribed in mitosis.  We also know that the “activators” of the MBF complex are different depending on the set of genes: either Rep1 for the “recombination” genes or Rep2 for the rest of the MBF-dependent genes.  But how the MBF complex is re-directed to a completely new set of genes during meiosis and the role of the “activators” and that of other chromatin modifiers, is still unknown.  We plan to characterize the molecular events that take place to re-direct MBF to these new genes.

 

Research identification links

https://www.ncbi.nlm.nih.gov/sites/myncbi/1T1eacyItla5r/bibliography/53577909/public/?sort=date&direction=ascending

ORCID ID: 0000-0002-6354-0536
Researcher ID: L-5217-2014

Group website: https://www.upf.edu/web/osccg

Personal website: https://www.upf.edu/web/osccg/entry/-/-/10011/adscripcion/jose-ayte