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Article ; Online: Maintaining transcriptional homeostasis during cell cycle.

Ramos-Alonso, Lucía / Chymkowitch, Pierre

2023 Volume 15, Issue 1-2, Page(s) 1–21

Abstract: The preservation of gene expression patterns that define cellular identity throughout the cell division cycle is essential to perpetuate cellular lineages. However, the progression of cells through different phases of the cell cycle severely disrupts ... ...

Abstract	The preservation of gene expression patterns that define cellular identity throughout the cell division cycle is essential to perpetuate cellular lineages. However, the progression of cells through different phases of the cell cycle severely disrupts chromatin accessibility, epigenetic marks, and the recruitment of transcriptional regulators. Notably, chromatin is transiently disassembled during S-phase and undergoes drastic condensation during mitosis, which is a significant challenge to the preservation of gene expression patterns between cell generations. This article delves into the specific gene expression and chromatin regulatory mechanisms that facilitate the preservation of transcriptional identity during replication and mitosis. Furthermore, we emphasize our recent findings revealing the unconventional role of yeast centromeres and mitotic chromosomes in maintaining transcriptional fidelity beyond mitosis.
MeSH term(s)	Cell Cycle/genetics ; Centromere/metabolism ; Centromere/genetics ; Chromatin/metabolism ; Chromatin/genetics ; Homeostasis/genetics ; Mitosis/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Transcription, Genetic/genetics
Language	English
Publishing date	2023-09-01
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2646974-1
ISSN	2154-1272 ; 2154-1264
ISSN (online)	2154-1272
ISSN	2154-1264
DOI	10.1080/21541264.2023.2246868
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Analysis of the pheromone signaling pathway by RT-qPCR in the budding yeast

Ramos-Alonso, Lucía / Garcia, Ignacio / Enserink, Jorrit M / Chymkowitch, Pierre

STAR protocols

2022 Volume 3, Issue 1, Page(s) 101210

Abstract: ... ...

Abstract	FUS3
MeSH term(s)	Mitogen-Activated Protein Kinases/metabolism ; Pheromones/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics ; Signal Transduction/genetics ; Yeast, Dried
Chemical Substances	Pheromones ; Saccharomyces cerevisiae Proteins ; FUS3 protein, S cerevisiae (EC 2.7.11.24) ; Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	English
Publishing date	2022-03-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2022.101210
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Article ; Online: Characterization of a selective, iron-chelating antifungal compound that disrupts fungal metabolism and synergizes with fluconazole.

Corrales, Jeanne / Ramos-Alonso, Lucia / González-Sabín, Javier / Ríos-Lombardía, Nicolás / Trevijano-Contador, Nuria / Engen Berg, Henriette / Sved Skottvoll, Frøydis / Moris, Francisco / Zaragoza, Oscar / Chymkowitch, Pierre / Garcia, Ignacio / Enserink, Jorrit M

Microbiology spectrum

2024 Volume 12, Issue 2, Page(s) e0259423

Abstract: Fungal infections are a growing global health concern due to the limited number of available antifungal therapies as well as the emergence of fungi that are resistant to first-line antimicrobials, particularly azoles and echinocandins. Development of ... ...

Abstract	Fungal infections are a growing global health concern due to the limited number of available antifungal therapies as well as the emergence of fungi that are resistant to first-line antimicrobials, particularly azoles and echinocandins. Development of novel, selective antifungal therapies is challenging due to similarities between fungal and mammalian cells. An attractive source of potential antifungal treatments is provided by ecological niches co-inhabited by bacteria, fungi, and multicellular organisms, where complex relationships between multiple organisms have resulted in evolution of a wide variety of selective antimicrobials. Here, we characterized several analogs of one such natural compound, collismycin A. We show that NR-6226C has antifungal activity against several pathogenic
MeSH term(s)	Animals ; Humans ; Antifungal Agents/pharmacology ; Fluconazole/pharmacology ; Iron ; Candida ; Mycoses/microbiology ; Candida albicans ; Anti-Infective Agents/pharmacology ; Azoles/pharmacology ; Candida glabrata ; Iron Chelating Agents/pharmacology ; Drug Resistance, Fungal ; Microbial Sensitivity Tests ; Mammals
Chemical Substances	Antifungal Agents ; Fluconazole (8VZV102JFY) ; Iron (E1UOL152H7) ; Anti-Infective Agents ; Azoles ; Iron Chelating Agents
Language	English
Publishing date	2024-01-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.02594-23
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Article: Iron Regulatory Mechanisms in

Ramos-Alonso, Lucía / Romero, Antonia María / Martínez-Pastor, María Teresa / Puig, Sergi

Frontiers in microbiology

2020 Volume 11, Page(s) 582830

Abstract: Iron is an essential micronutrient for all eukaryotic organisms because it participates as a redox cofactor in many cellular processes. However, excess iron can damage cells since it promotes the generation of reactive oxygen species. The budding ... ...

Abstract	Iron is an essential micronutrient for all eukaryotic organisms because it participates as a redox cofactor in many cellular processes. However, excess iron can damage cells since it promotes the generation of reactive oxygen species. The budding yeast
Language	English
Publishing date	2020-09-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2020.582830
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Article ; Online: Global translational repression induced by iron deficiency in yeast depends on the Gcn2/eIF2α pathway.

Romero, Antonia María / Ramos-Alonso, Lucía / Alepuz, Paula / Puig, Sergi / Martínez-Pastor, María Teresa

Scientific reports

2020 Volume 10, Issue 1, Page(s) 233

Abstract: Iron is an essential element for all eukaryotic organisms because it participates as a redox active cofactor in a wide range of biological processes, including protein synthesis. Translation is probably the most energy consuming process in cells. ... ...

Abstract	Iron is an essential element for all eukaryotic organisms because it participates as a redox active cofactor in a wide range of biological processes, including protein synthesis. Translation is probably the most energy consuming process in cells. Therefore, one of the initial responses of eukaryotic cells to stress or nutrient limitation is the arrest of mRNA translation. In first instance, the budding yeast Saccharomyces cerevisiae responds to iron deficiency by activating iron acquisition and remodeling cellular metabolism in order to prioritize essential over non-essential iron-dependent processes. We have determined that, despite a global decrease in transcription, mRNA translation is actively maintained during a short-term exposure to iron scarcity. However, a more severe iron deficiency condition induces a global repression of translation. Our results indicate that the Gcn2-eIF2α pathway limits general translation at its initiation step during iron deficiency. This bulk translational inhibition depends on the uncharged tRNA sensing Gcn1-Gcn20 complex. The involvement of the Gcn2-eIF2α pathway in the response to iron deficiency highlights its central role in the eukaryotic response to stress or nutritional deprivation, which is conserved from yeast to mammals.
MeSH term(s)	Eukaryotic Initiation Factor-2/metabolism ; Iron/deficiency ; Protein Biosynthesis ; Protein-Serine-Threonine Kinases/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/metabolism
Chemical Substances	Eukaryotic Initiation Factor-2 ; SUI2 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins ; Iron (E1UOL152H7) ; GCN2 protein, S cerevisiae (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2020-01-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-57132-0
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Article ; Online: Mitotic chromosome condensation resets chromatin to safeguard transcriptional homeostasis during interphase.

Ramos-Alonso, Lucía / Holland, Petter / Le Gras, Stéphanie / Zhao, Xu / Jost, Bernard / Bjørås, Magnar / Barral, Yves / Enserink, Jorrit M / Chymkowitch, Pierre

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 4, Page(s) e2210593120

Abstract: Mitotic entry correlates with the condensation of the chromosomes, changes in histone modifications, exclusion of transcription factors from DNA, and the broad downregulation of transcription. However, whether mitotic condensation influences ... ...

Abstract	Mitotic entry correlates with the condensation of the chromosomes, changes in histone modifications, exclusion of transcription factors from DNA, and the broad downregulation of transcription. However, whether mitotic condensation influences transcription in the subsequent interphase is unknown. Here, we show that preventing one chromosome to condense during mitosis causes it to fail resetting of transcription. Rather, in the following interphase, the affected chromosome contains unusually high levels of the transcription machinery, resulting in abnormally high expression levels of genes
MeSH term(s)	Chromatin/genetics ; Chromosomes/genetics ; Chromosomes/metabolism ; Interphase/genetics ; Mitosis/genetics ; Transcription Factors/metabolism
Chemical Substances	Chromatin ; Transcription Factors
Language	English
Publishing date	2023-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2210593120
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Article: Dissecting mRNA decay and translation inhibition during iron deficiency

Ramos-Alonso, Lucía / Antonia María Romero / Julio Polaina / Sergi Puig / María Teresa Martínez-Pastor

Current genetics. 2019 Feb., v. 65, no. 1

2019

Abstract: Iron participates as a vital cofactor in multiple metabolic pathways. Despite its abundance, iron bioavailability is highly restricted in aerobic and alkaline environments. Therefore, living organisms have evolved multiple adaptive mechanisms to respond ... ...

Abstract	Iron participates as a vital cofactor in multiple metabolic pathways. Despite its abundance, iron bioavailability is highly restricted in aerobic and alkaline environments. Therefore, living organisms have evolved multiple adaptive mechanisms to respond to iron scarcity. These strategies include a global remodeling of iron metabolism directed to optimize iron utilization. In the baker’s yeast Saccharomyces cerevisiae, this metabolic reorganization is accomplished to a large extent by an mRNA-binding protein called Cth2. Yeast Cth2 belongs to a conserved family of tandem zinc finger containing proteins that specifically bind to transcripts with AU-rich elements and promote their turnover. A recent study has revealed that Cth2 also inhibits the translation of its target mRNAs (Ramos-Alonso et al., PLoS Genet 14:e1007476, https://doi.org/10.1371/journal.pgen.1007476 , 2018). Interestingly, the mammalian Cth2 ortholog known as tristetraprolin (aka TTP/TIS11/ZFP36), which is also implicated in controlling iron metabolism, promotes the decay and prevents the translation of its regulated transcripts. These observations open the possibility to study the relative contribution of altering mRNA stability and translation to the physiological adaptation to iron deficiency, the function played by the different domains within the mRNA-binding protein, and the potential factors implicated in coordinating both post-transcriptional events.
Keywords	Saccharomyces cerevisiae ; bioavailability ; biochemical pathways ; iron ; iron absorption ; mammals ; messenger RNA ; nutrient deficiencies ; proteins ; translation (genetics) ; yeasts ; zinc finger motif
Language	English
Dates of publication	2019-02
Size	p. 139-145.
Publishing place	Springer Berlin Heidelberg
Document type	Article
Note	Review
ZDB-ID	282876-5
ISSN	1432-0983 ; 0172-8083
ISSN (online)	1432-0983
ISSN	0172-8083
DOI	10.1007/s00294-018-0880-2
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Article ; Online: Waves of sumoylation support transcription dynamics during adipocyte differentiation.

Zhao, Xu / Hendriks, Ivo A / Le Gras, Stéphanie / Ye, Tao / Ramos-Alonso, Lucía / Nguéa P, Aurélie / Lien, Guro Flor / Ghasemi, Fatemeh / Klungland, Arne / Jost, Bernard / Enserink, Jorrit M / Nielsen, Michael L / Chymkowitch, Pierre

Nucleic acids research

2022 Volume 50, Issue 3, Page(s) 1351–1369

Abstract: Tight control of gene expression networks required for adipose tissue formation and plasticity is essential for adaptation to energy needs and environmental cues. However, the mechanisms that orchestrate the global and dramatic transcriptional changes ... ...

Abstract	Tight control of gene expression networks required for adipose tissue formation and plasticity is essential for adaptation to energy needs and environmental cues. However, the mechanisms that orchestrate the global and dramatic transcriptional changes leading to adipocyte differentiation remain to be fully unraveled. We investigated the regulation of nascent transcription by the sumoylation pathway during adipocyte differentiation using SLAMseq and ChIPseq. We discovered that the sumoylation pathway has a dual function in differentiation; it supports the initial downregulation of pre-adipocyte-specific genes, while it promotes the establishment of the mature adipocyte transcriptional program. By characterizing endogenous sumoylome dynamics in differentiating adipocytes by mass spectrometry, we found that sumoylation of specific transcription factors like PPARγ/RXR and their co-factors are associated with the transcription of adipogenic genes. Finally, using RXR as a model, we found that sumoylation may regulate adipogenic transcription by supporting the chromatin occurrence of transcription factors. Our data demonstrate that the sumoylation pathway supports the rewiring of transcriptional networks required for formation of functional adipocytes. This study also provides the scientists in the field of cellular differentiation and development with an in-depth resource of the dynamics of the SUMO-chromatin landscape, SUMO-regulated transcription and endogenous sumoylation sites during adipocyte differentiation.
MeSH term(s)	Adipocytes/metabolism ; Adipogenesis/genetics ; Cell Differentiation/genetics ; Chromatin/genetics ; Chromatin/metabolism ; Sumoylation ; Transcription Factors/metabolism
Chemical Substances	Chromatin ; Transcription Factors
Language	English
Publishing date	2022-01-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkac027
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Article ; Online: The yeast Aft1 transcription factor activates ribonucleotide reductase catalytic subunit RNR1 in response to iron deficiency.

Ros-Carrero, Cristina / Ramos-Alonso, Lucía / Romero, Antonia María / Bañó, M Carmen / Martínez-Pastor, María Teresa / Puig, Sergi

Biochimica et biophysica acta. Gene regulatory mechanisms

2020 Volume 1863, Issue 7, Page(s) 194522

Abstract: Eukaryotic ribonucleotide reductases are iron-dependent enzymes that catalyze the rate-limiting step in the de novo synthesis of deoxyribonucleotides. Multiple mechanisms regulate the activity of ribonucleotide reductases in response to genotoxic ... ...

Abstract	Eukaryotic ribonucleotide reductases are iron-dependent enzymes that catalyze the rate-limiting step in the de novo synthesis of deoxyribonucleotides. Multiple mechanisms regulate the activity of ribonucleotide reductases in response to genotoxic stresses and iron deficiency. Upon iron starvation, the Saccharomyces cerevisiae Aft1 transcription factor specifically binds to iron-responsive cis elements within the promoter of a group of genes, known as the iron regulon, activating their transcription. Members of the iron regulon participate in iron acquisition, mobilization and recycling, and trigger a genome-wide metabolic remodeling of iron-dependent pathways. Here, we describe a mechanism that optimizes the activity of yeast ribonucleotide reductase when iron is scarce. We demonstrate that Aft1 and the DNA-binding protein Ixr1 enhance the expression of the gene encoding for its catalytic subunit, RNR1, in response to iron limitation, leading to an increase in both mRNA and protein levels. By mutagenesis of the Aft1-binding sites within RNR1 promoter, we conclude that RNR1 activation by iron depletion is important for Rnr1 protein and deoxyribonucleotide synthesis. Remarkably, Aft1 also activates the expression of IXR1 upon iron scarcity through an iron-responsive element located within its promoter. These results provide a novel mechanism for the direct activation of ribonucleotide reductase function by the iron-regulated Aft1 transcription factor.
MeSH term(s)	DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Gene Expression Regulation, Fungal ; High Mobility Group Proteins/genetics ; High Mobility Group Proteins/metabolism ; Iron/deficiency ; Iron/metabolism ; Protein Binding ; Response Elements ; Ribonucleotide Reductases/genetics ; Ribonucleotide Reductases/metabolism ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcriptional Activation
Chemical Substances	AFT1 protein, S cerevisiae ; DNA-Binding Proteins ; High Mobility Group Proteins ; IXR1 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins ; Transcription Factors ; Iron (E1UOL152H7) ; Ribonucleotide Reductases (EC 1.17.4.-) ; Rnr1 protein, S cerevisiae (EC 1.17.4.-)
Language	English
Publishing date	2020-03-06
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2918786-2
ISSN	1876-4320 ; 1874-9399
ISSN (online)	1876-4320
ISSN	1874-9399
DOI	10.1016/j.bbagrm.2020.194522
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Article ; Online: Dissecting mRNA decay and translation inhibition during iron deficiency.

Ramos-Alonso, Lucía / Romero, Antonia María / Polaina, Julio / Puig, Sergi / Martínez-Pastor, María Teresa

Current genetics

2018 Volume 65, Issue 1, Page(s) 139–145

Abstract	Iron participates as a vital cofactor in multiple metabolic pathways. Despite its abundance, iron bioavailability is highly restricted in aerobic and alkaline environments. Therefore, living organisms have evolved multiple adaptive mechanisms to respond to iron scarcity. These strategies include a global remodeling of iron metabolism directed to optimize iron utilization. In the baker's yeast Saccharomyces cerevisiae, this metabolic reorganization is accomplished to a large extent by an mRNA-binding protein called Cth2. Yeast Cth2 belongs to a conserved family of tandem zinc finger containing proteins that specifically bind to transcripts with AU-rich elements and promote their turnover. A recent study has revealed that Cth2 also inhibits the translation of its target mRNAs (Ramos-Alonso et al., PLoS Genet 14:e1007476, https://doi.org/10.1371/journal.pgen.1007476 , 2018). Interestingly, the mammalian Cth2 ortholog known as tristetraprolin (aka TTP/TIS11/ZFP36), which is also implicated in controlling iron metabolism, promotes the decay and prevents the translation of its regulated transcripts. These observations open the possibility to study the relative contribution of altering mRNA stability and translation to the physiological adaptation to iron deficiency, the function played by the different domains within the mRNA-binding protein, and the potential factors implicated in coordinating both post-transcriptional events.
MeSH term(s)	Adaptation, Physiological/genetics ; Animals ; Gene Expression Regulation, Fungal ; Humans ; Iron/metabolism ; Protein Biosynthesis ; RNA Stability ; RNA, Fungal/genetics ; RNA, Fungal/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Tristetraprolin/genetics ; Tristetraprolin/metabolism
Chemical Substances	RNA, Fungal ; Saccharomyces cerevisiae Proteins ; TIS11 protein, S cerevisiae ; Tristetraprolin ; Iron (E1UOL152H7)
Language	English
Publishing date	2018-08-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	282876-5
ISSN	1432-0983 ; 0172-8083
ISSN (online)	1432-0983
ISSN	0172-8083
DOI	10.1007/s00294-018-0880-2
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