المؤلفون: Laurent, Marc-Charles

مرشدي الرسالة: West, Gale E., Cloutier, Jacinthe

مصطلحات موضوعية: Exploitations agricoles, Québec (Province), Cultures, Agriculture, Aspect de l'environnement, Bonnes pratiques.

جغرافية الموضوع: Québec (Province)

الوصف: Titre de l'écran-titre (visionné le 10 janvier 2024)
Un grand nombre d'auteurs et d'institutions gouvernementales s'entendent pour dire que l'agriculture est devenue problématique pour l'environnement à la suite de son industrialisation, vers les années 1950, alors que s'est effectuée la transition d'une agriculture extensive à une agriculture très productive avec une forte consommation d'intrants (Nature Québec, 2011; Ministère de l'Environnement, de la Lutte contre les changements climatiques, de la Faune et des Parcs (MELCCFP), 2003; Leblanc, 2010; Ministère des Ressources naturelles et des Forêts (MRNF), 2007). Ces problèmes écologiques liés à l'agriculture sont également partagés par plusieurs pays dans le monde (Reimer et Prokopy, 2014) et sont parmi les plus inquiétants en Europe et en Amérique du Nord. Beaucoup de mesures sont mises en place pour faire adopter davantage de bonnes pratiques agroenvironnementales par les producteurs agricoles québécois. Un questionnaire Web a été administré à 284 producteurs œuvrant dans le secteur végétal des régions de Chaudière-Appalaches, Centre-du-Québec et Montérégie. Une régression multiple des moindres carrés ordinaire (MCO) a été conduite afin de mettre en relief l'effet de certains leviers d'action menant à une adoption élargie des bonnes pratiques agroenvironnementales. Les résultats ont montré un impact statistiquement significatif pour ce qui est de l'intérêt des producteurs envers les informations liées aux bonnes pratiques agroenvironnementales (BPA) ainsi qu'au fait d'utiliser ces informations. La perception par rapport à l'accessibilité envers les intrants moins nocifs et la participation au plan d'accompagnement agroenvironnemental (PAA) se sont également avérées significatives avec le score d'adoption. En résumé, les leviers informationnels et d'accompagnement ont été trouvés comme étant les plus efficaces pour susciter l'acte d'adoption vers de meilleures pratiques agroenvironnementales. Cette recherche montre que le processus d'adoption est complexe, mais qu'il existe des solutions tangibles et efficaces pour sensibiliser et aider les agriculteurs dans leurs démarches d'adoption.
Many authors and government institutions agree that agriculture became problematic for the environment following its industrialization in the 1950s, when the transition from extensive agriculture to highly productive agriculture with high input consumption took place (Nature Québec, 2011, Ministère de l'Environnement, de la Lutte contre les changements climatiques, de la Faune et des Parcs (MELCCFP), 2003; Leblanc, 2010; Ministère des Ressources naturelles et des Forêts (MRNF), 2007). These ecological problems related to agriculture are also shared by several countries around the world (Reimer and Prokopy, 2014) and are among the most worrisome in Europe and North America. Many measures are put in place to get more agri-environmental best practices adopted by Quebec farmers. A web questionnaire was administered to 284 producers working in the plant sector in the Chaudière-Appalaches, Centre-du- Québec and Montérégie regions. An ordinary least squares (OLS) regression was conducted with the aim of highlighting the levers of action leading to a wider adoption of agri-environmental good practices. The results showed a statistically significant impact in terms of producers' interest in and using the information related to good agri-environmental practices. Perceived accessibility to less harmful inputs and participation in the agri-environmental support plan were also significant with the adoption score. Informational and accompanying levers have been found to be the most effective in driving the act of adoption towards better agri-environmental practices. This research shows that the adoption process is complex, but that there are tangible and effective solutions to raise awareness and assist farmers in the adoption process.

وصف الملف: 1 ressource en ligne (xi, 124 pages); application/pdf

الإتاحة: http://hdl.handle.net/20.500.11794/132164Test

المؤلفون: Washington, Nicole L, Gangavarapu, Karthik, Zeller, Mark, Bolze, Alexandre, Cirulli, Elizabeth T, Schiabor Barrett, Kelly M, Larsen, Brendan B, Anderson, Catelyn, White, Simon, Cassens, Tyler, Jacobs, Sharoni, Levan, Geraint, Nguyen, Jason, Ramirez, Jimmy M, Rivera-Garcia, Charlotte, Sandoval, Efren, Wang, Xueqing, Wong, David, Spencer, Emily, Robles-Sikisaka, Refugio, Kurzban, Ezra, Hughes, Laura D, Deng, Xianding, Wang, Candace, Servellita, Venice, Valentine, Holly, De Hoff, Peter, Seaver, Phoebe, Sathe, Shashank, Gietzen, Kimberly, Sickler, Brad, Antico, Jay, Hoon, Kelly, Liu, Jingtao, Harding, Aaron, Bakhtar, Omid, Basler, Tracy, Austin, Brett, MacCannell, Duncan, Isaksson, Magnus, Febbo, Phillip G, Becker, David, Laurent, Marc, McDonald, Eric, Yeo, Gene W, Knight, Rob, Laurent, Louise C, de Feo, Eileen, Worobey, Michael, Chiu, Charles Y, Suchard, Marc A, Lu, James T, Lee, William, Andersen, Kristian G

المصدر: Cell. 184(10)

مصطلحات موضوعية: Humans, Models, Biological, United States, Female, Male, COVID-19, SARS-CoV-2, 501Y.V1, B.1.1.7, VOC-202012/01, genomic epidemiology, variant of concern, Vaccine Related, Genetics, Human Genome, Biodefense, Prevention, Lung, Pneumonia, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Developmental Biology

الوصف: The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has gained a foothold across the world. Using S gene target failure (SGTF) and SARS-CoV-2 genomic sequencing, we investigated the prevalence and dynamics of this variant in the United States (US), tracking it back to its early emergence. We found that, while the fraction of B.1.1.7 varied by state, the variant increased at a logistic rate with a roughly weekly doubling rate and an increased transmission of 40%-50%. We revealed several independent introductions of B.1.1.7 into the US as early as late November 2020, with community transmission spreading it to most states within months. We show that the US is on a similar trajectory as other countries where B.1.1.7 became dominant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2rw0t09qTest

المؤلفون: Washington, Nicole L, Gangavarapu, Karthik, Zeller, Mark, Bolze, Alexandre, Cirulli, Elizabeth T, Barrett, Kelly M Schiabor, Larsen, Brendan B, Anderson, Catelyn, White, Simon, Cassens, Tyler, Jacobs, Sharoni, Levan, Geraint, Nguyen, Jason, Ramirez, Jimmy M, Rivera-Garcia, Charlotte, Sandoval, Efren, Wang, Xueqing, Wong, David, Spencer, Emily, Robles-Sikisaka, Refugio, Kurzban, Ezra, Hughes, Laura D, Deng, Xianding, Wang, Candace, Servellita, Venice, Valentine, Holly, De Hoff, Peter, Seaver, Phoebe, Sathe, Shashank, Gietzen, Kimberly, Sickler, Brad, Antico, Jay, Hoon, Kelly, Liu, Jingtao, Harding, Aaron, Bakhtar, Omid, Basler, Tracy, Austin, Brett, Isaksson, Magnus, Febbo, Phillip G, Becker, David, Laurent, Marc, McDonald, Eric, Yeo, Gene W, Knight, Rob, Laurent, Louise C, de Feo, Eileen, Worobey, Michael, Chiu, Charles, Suchard, Marc A, Lu, James T, Lee, William, Andersen, Kristian G

المصدر: medRxiv. 2(02-09)

مصطلحات موضوعية: Vaccine Related, Prevention, Biodefense, Lung, Good Health and Well Being

الوصف: As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2pk2j6sdTest

المؤلفون: Laurent, Marc

مرشدي الرسالة: Sorbonne Paris Cité, Prioleau, Marie-Noëlle

مصطلحات موضوعية: Motifs G4, Lignée DT40, G4 motifs, DT40 cell line

الوصف: Les origines de réplication sont les sites à travers le génome où est initiée la synthèse de l’ADN. Les multiples cartographies des origines de réplication dans des cellules de vertébrés ont identifié une association entre origines de réplication et motifs G4. Les motifs G4 sont des séquences ayant le potentiel de se replier en G-quadruplexe. Des travaux menés précédemment au laboratoire ont montré que la capacité d’un motif G4 à se replier en G-quadruplexe est essentielle pour l’activité de deux origines de réplication modèles dans la lignée cellulaire de poulet DT40. Cependant, le motif G4 n’est pas suffisant pour spécifier une origine de réplication. Dans l’origine modèle βA, un élément cis de 227 pben 3’ du motif G4 est également nécessaire pour l’initiation de la réplication. L’analyse de la séquence de cet élément indique qu’il comporte plusieurs motifs connus pour être des sites de fixation de facteurs de transcription. Nous avons testé le rôle potentiel de ces motifs en évaluant l’effet de leurs délétions individuelles sur l’activité de l’origine βA. Ces travaux ont identifié les boites TATA et CCAAT, pouvant être liées par le facteur TBP (TATA Binding Protein) et NFY (Nuclear Factor Y) respectivement, comme étant les éléments cruciaux avec le motif G4 pour l’initiation de la réplication. Nous avons cherché à éclaircir de quelle manière ces éléments permettent la spécification d’une origine de réplication. A cet effet, nous avons émis l’hypothèse selon laquelle les motifs G4 qui se trouvent au niveau des origines de réplication sont ceux qui in vivo sont capables de former un G-quadruplexe. La formation du G-quadruplex dans l’origine βA dépendrait alors de la présence des boites TATA et CCAAT qui peuvent recruter des facteurs de transcription favorisant l’ouverture de la double hélice de l’ADN et le repliement du G-quadruplex. Cette hypothèse prévoit que la stabilisation d’un G-quadruplexe in vivo est nécessaire et suffisante pour former une nouvelle origine de réplication. Nous avons donc testé cette hypothèse de deux manières. D’abord, nous avons entrepris de stabiliser un G-quadruplex à une position donnée du génome en induisant la transcription d’un motif G4. Ensuite, nous avons déterminé les effets d’une stabilisation globale des G-quadruplexes à travers le génome sur la position des origines de réplication. Pour cela, nous avons cartographié les origines de réplication dans des lignées de cellules DT40 dans lesquelles des facteurs impliqués dans la linéarisation des G-quadruplexes ont été inactivés. Selon notre hypothèse, en l’absence de tels facteurs, comme l’hélicase FancJ ou l’ADN polymérase translésionnelle Rev1, davantage de motifs G4 pourraient se replier et former une origine de réplication. Les résultats obtenus avec chacune des deux approches indiquent que la stabilisation de G-quadruplexes ne permet pas de produire de nouvelles origines de réplication. L’ensemble de nos données indique que l’activité de l’origine βA dépend d’un motif G4 et des boites TATA et CCAAT. La manière par laquelle l’ensemble de ces éléments permettent l’initiation de la réplication reste à éclaircir
Replication origins are the position where DNA synthesis is initiated. Mapping of replication origins across the genome showed a link between origins and G4 motifs. G4 motifs are sequences the potential for forming G-quadruplexes. Works carried out previously in the laboratory showed that the ability to fold into G-quadruplex is critical for the activity of two model origin in the DT40 cell line. However, the G4 motif is not enough to specify a replication origin. In the βA model origin, a 227 bp cis element is required for the initiation of replication. The analysis of this sequence indicates the presence of several motifs known to be binding sites for transcription factors. We tested the potential roles of these motifs by evaluating the effect of their individual deletion on the activity of the βA origin. This work identified the TATA and CCAAT boxes who bind TBP (TATA Binding Protein) and NFY (Nuclear Factor Y) respectively as the crucial elements, with the G4 motifs, pour the initiation of replication.We endeavored to shed light on the manner by which these elements enable the specification of a replication origin. We hypothesized that the G4 motifs associated with replication origins are those able to form a G-quadruplex in vivo. The formation of the G-quadruplex of the βA origin would require the presence of the TATA and CCAAT boxes who could recruit transcription factors facilitating the opening of the double helix and G-quadruplex folding. We tested this hypothesis by two different manners. First, we undertook to stabilize a G-quadruplex at a given position in the genome by inducing the transcription of a G4 motif. Then, we observed the effects of a genome wide stabilization of G-quadruplexes on the position of replication origins. For that, we mapped replication origins in DT40 cell lines in which factors implicated in G-quadruplex linearization are inactivated. According to our hypothesis, without such factors, like the FancJ helicase of the translesional DNA polymerase Rev1, more G4 motifs could fold into G-quaduplexes and specify replication origins

الإتاحة: http://www.theses.fr/2016USPCC162/documentTest

المؤلفون: Poulet-Benedetti, Jérémy, Tonnerre-Doncarli, Caroline, Valton, Anne-Laure, Laurent, Marc, Gérard, Marie, Barinova, Natalja, Parisis, Nikolaos, Massip, Florian, Picard, Franck, Prioleau, Marie-Noëlle

المساهمون: Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut Curie Paris -Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Bioinformatique (CBIO), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

المصدر: ISSN: 2041-1723.

مصطلحات موضوعية: [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]

الوصف: International audience ; Replication of vertebrate genomes is tightly regulated to ensure accurate duplication, but our understanding of the interplay between genetic and epigenetic factors in this regulation remains incomplete. Here, we investigated the involvement of three elements enriched at gene promoters and replication origins: guanine-rich motifs potentially forming G-quadruplexes (pG4s), nucleosome-free regions (NFRs), and the histone variant H2A.Z, in the firing of origins of replication in vertebrates. We show that two pG4s on the same DNA strand (dimeric pG4s) are sufficient to induce the assembly of an efficient minimal replication origin without inducing transcription in avian DT40 cells. Dimeric pG4s in replication origins are associated with formation of an NFR next to precisely-positioned nucleosomes enriched in H2A.Z on this minimal origin and genome-wide. Thus, our data suggest that dimeric pG4s are important for the organization and duplication of vertebrate genomes. It supports the hypothesis that a nucleosome close to an NFR is a shared signal for the formation of replication origins in eukaryotes.

العلاقة: hal-04184349; https://hal.science/hal-04184349Test; https://hal.science/hal-04184349/documentTest; https://hal.science/hal-04184349/file/s41467-023-40441-4.pdfTest

الإتاحة: https://doi.org/10.1038/s41467-023-40441-4Test
https://hal.science/hal-04184349Test
https://hal.science/hal-04184349/documentTest
https://hal.science/hal-04184349/file/s41467-023-40441-4.pdfTest

المؤلفون: Brossas, Caroline, Valton, Anne-Laure, Venev, Sergey V., Chilaka, Sabarinadh, Counillon, Antonin, Laurent, Marc, Goncalves, Coralie, Duriez, Benedicte, Picard, Franck, Dekker, Job, Prioleau, Marie-Noelle

المساهمون: Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology

المصدر: The EMBO journal ; 39 ; 21 ; e99520

مصطلحات موضوعية: chromatin accessibility, nuclear organization, promoter, replication origin, replication timing, Biochemistry, Biophysics, and Structural Biology, Genetics and Genomics, Systems Biology

الوصف: Vertebrate genomes replicate according to a precise temporal program strongly correlated with their organization into A/B compartments. Until now, the molecular mechanisms underlying the establishment of early-replicating domains remain largely unknown. We defined two minimal cis-element modules containing a strong replication origin and chromatin modifier binding sites capable of shifting a targeted mid-late-replicating region for earlier replication. The two origins overlap with a constitutive or a silent tissue-specific promoter. When inserted side-by-side, these modules advance replication timing over a 250 kb region through the cooperation with one endogenous origin located 30 kb away. Moreover, when inserted at two chromosomal sites separated by 30 kb, these two modules come into close physical proximity and form an early-replicating domain establishing more contacts with active A compartments. The synergy depends on the presence of the active promoter/origin. Our results show that clustering of strong origins located at active promoters can establish early-replicating domains.

العلاقة: Link to Article in PubMed; Brossas C, Valton AL, Venev SV, Chilaka S, Counillon A, Laurent M, Goncalves C, Duriez B, Picard F, Dekker J, Prioleau MN. Clustering of strong replicators associated with active promoters is sufficient to establish an early-replicating domain. EMBO J. 2020 Nov 2;39(21):e99520. doi:10.15252/embj.201899520. Epub 2020 Sep 16. PMID: 32935369; PMCID: PMC7604622. Link to article on publisher's site; 0261-4189 (Linking); http://hdl.handle.net/20.500.14038/41665Test; https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5486&context=oapubs&unstamped=1Test; https://escholarship.umassmed.edu/oapubs/4456Test; oapubs/4456

الإتاحة: https://doi.org/10.15252/embj.201899520Test
https://doi.org/20.500.14038/41665Test
https://hdl.handle.net/20.500.14038/41665Test
https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5486&context=oapubs&unstamped=1Test
https://escholarship.umassmed.edu/oapubs/4456Test

المؤلفون: Bolze, Alexandre, Luo, Shishi, White, Simon, Cirulli, Elizabeth T., Wyman, Dana, Dei Rossi, Andrew, Machado, Henrique, Cassens, Tyler, Jacobs, Sharoni, Schiabor Barrett, Kelly M., Tanudjaja, Francisco, Tsan, Kevin, Nguyen, Jason, Ramirez, Jimmy M., Sandoval, Efren, Wang, Xueqing, Wong, David, Becker, David, Laurent, Marc, Lu, James T., Isaksson, Magnus, Washington, Nicole L., Lee, William

المصدر: Cell Reports Medicine ; volume 3, issue 3, page 100564 ; ISSN 2666-3791

مصطلحات موضوعية: General Biochemistry, Genetics and Molecular Biology

الإتاحة: https://doi.org/10.1016/j.xcrm.2022.100564Test
https://api.elsevier.com/content/article/PII:S2666379122000714?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2666379122000714?httpAccept=text/plainTest

المؤلفون: Buisine, Nicolas, Grimaldi, Alexis, Jonchere, Vincent, Rigolet, Muriel, Blugeon, Corinne, Hamroune, Juliette, Sachs, Laurent Marc

المساهمون: Physiologie moléculaire et adaptation (PhyMA), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), GenomiqueENS (Genomique ENS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-10-INBS-0009,France Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)

المصدر: ISSN: 2073-4409 ; Cells ; https://hal.science/hal-03364443Test ; Cells, 2021, 10 (9), pp.2375. ⟨10.3390/cells10092375⟩.

مصطلحات موضوعية: Xenopus metamorphosis, thyroid hormone, glucocorticoids, cross-talks, functional genomics, DNA methylation, [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology

الوصف: International audience ; Background: Most work in endocrinology focus on the action of a single hormone, and very little on the cross-talks between two hormones. Here we characterize the nature of interactions between thyroid hormone and glucocorticoid signaling during Xenopus tropicalis metamorphosis. Methods: We used functional genomics to derive genome wide profiles of methylated DNA and measured changes of gene expression after hormonal treatments of a highly responsive tissue, tailfin. Clustering classified the data into four types of biological responses, and biological networks were modeled by system biology. Results: We found that gene expression is mostly regulated by either T3 or CORT, or their additive effect when they both regulate the same genes. A small but non-negligible fraction of genes (12%) displayed non-trivial regulations indicative of complex interactions between the signaling pathways. Strikingly, DNA methylation changes display the opposite and are dominated by cross-talks. Conclusion: Cross-talks between thyroid hormones and glucocorticoids are more complex than initially envisioned and are not limited to the simple addition of their individual effects, a statement that can be summarized with the pseudo-equation: TH ∙ GC > TH + GC. DNA methylation changes are highly dynamic and buffered from genome expression.

العلاقة: hal-03364443; https://hal.science/hal-03364443Test; https://hal.science/hal-03364443/documentTest; https://hal.science/hal-03364443/file/2021-cells.pdfTest

الإتاحة: https://doi.org/10.3390/cells10092375Test
https://hal.science/hal-03364443Test
https://hal.science/hal-03364443/documentTest
https://hal.science/hal-03364443/file/2021-cells.pdfTest

المؤلفون: Nicolas Buisine, Alexis Grimaldi, Vincent Jonchere, Muriel Rigolet, Corinne Blugeon, Juliette Hamroune, Laurent Marc Sachs

المصدر: Cells, Vol 10, Iss 2375, p 2375 (2021)

مصطلحات موضوعية: Xenopus metamorphosis, thyroid hormone, glucocorticoids, cross-talks, functional genomics, DNA methylation, Cytology, QH573-671

الوصف: Background: Most work in endocrinology focus on the action of a single hormone, and very little on the cross-talks between two hormones. Here we characterize the nature of interactions between thyroid hormone and glucocorticoid signaling during Xenopus tropicalis metamorphosis. Methods: We used functional genomics to derive genome wide profiles of methylated DNA and measured changes of gene expression after hormonal treatments of a highly responsive tissue, tailfin. Clustering classified the data into four types of biological responses, and biological networks were modeled by system biology. Results: We found that gene expression is mostly regulated by either T 3 or CORT, or their additive effect when they both regulate the same genes. A small but non-negligible fraction of genes (12%) displayed non-trivial regulations indicative of complex interactions between the signaling pathways. Strikingly, DNA methylation changes display the opposite and are dominated by cross-talks. Conclusion: Cross-talks between thyroid hormones and glucocorticoids are more complex than initially envisioned and are not limited to the simple addition of their individual effects, a statement that can be summarized with the pseudo-equation: TH ∙ GC > TH + GC. DNA methylation changes are highly dynamic and buffered from genome expression.

العلاقة: https://www.mdpi.com/2073-4409/10/9/2375Test; https://doaj.org/toc/2073-4409Test; https://doaj.org/article/7f133dfe006c40ebab6c10a21cd0369eTest

الإتاحة: https://doi.org/10.3390/cells10092375Test
https://doaj.org/article/7f133dfe006c40ebab6c10a21cd0369eTest

المؤلفون: Laurent, Marc¹ (AUTHOR) marclaurent1988@gmail.com, Cordeddu, Lina¹ (AUTHOR), Zahedi, Yasaman¹ (AUTHOR), Ekwall, Karl¹ (AUTHOR) karl.ekwall@ki.se

المصدر: Biomolecules (2218-273X). Nov2023, Vol. 13 Issue 11, p1662. 17p.

مصطلحات موضوعية: *GENE expression, *GENETIC regulation, *ION transport (Biology), *FIBROBLASTS, *CALCIUM ions, *SLEEP deprivation, *SEED dormancy

مستخلص: (1) Background: The LEO1 (Left open reading frame 1) protein is a conserved subunit of the PAF1C complex (RNA polymerase II-associated factor 1 complex). PAF1C has well-established mechanistic functions in elongation of transcription and RNA processing. We previously showed, in fission yeast, that LEO1 controls histone H3K9 methylation levels by affecting the turnover of histone H3 in chromatin, and that it is essential for the proper regulation of gene expression during cellular quiescence. Human fibroblasts enter a reversible quiescence state upon serum deprivation in the growth media. Here we investigate the function of LEO1 in human fibroblasts. (2) Methods: We knocked out the LEO1 gene using CRISPR/Cas9 methodology in human fibroblasts and verified that the LEO1 protein was undetectable by Western blot. We characterized the phenotype of the ΔLEO1 knockout cells with FACS analysis and cell growth assays. We used RNA-sequencing using spike-in controls to measure gene expression and spike-in controlled ChIP-sequencing experiments to measure the histone modification H3K9me2 genome-wide. (3) Results: Gene expression levels are altered in quiescent cells, however factors controlling chromatin and gene expression changes in quiescent human cells are largely unknown. The ΔLEO1 knockout fibroblasts are viable but have reduced metabolic activity compared to wild-type cells. ΔLEO1 cells showed a slower entry into quiescence and a different morphology compared to wild-type cells. Gene expression was generally reduced in quiescent wild-type cells. The downregulated genes included genes involved in cell proliferation. A small number of genes were upregulated in quiescent wild-type cells including several genes involved in ERK1/ERK2 and Wnt signaling. In quiescent ΔLEO1 cells, many genes were mis-regulated compared to wild-type cells. This included genes involved in Calcium ion transport and cell morphogenesis. Finally, spike-in controlled ChIP-sequencing experiments demonstrated that the histone modification H3K9me2 levels are globally increased in quiescent ΔLEO1 cells. (4) Conclusions: Thus, LEO1 is important for proper entry into cellular quiescence, control of H3K9me2 levels, and gene expression in human fibroblasts. [ABSTRACT FROM AUTHOR]