The histone H2B Arg95 residue efficiently recruits the transcription factor Spt16 to mediate Ste5 expression of the pheromone response pathway

<p dir="ltr">In yeast Saccharomyces cerevisiae, the immunosuppressant rapamycin inhibits the TORC1 kinase causing rapid alteration in gene expression and leading to G1 arrest. We recently reported the isolation and characterization from the histone mutant collection of a histone H2B...

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التفاصيل البيبلوغرافية
المؤلف الرئيسي: Abdallah Alhaj Sulaiman (17777421) (author)
مؤلفون آخرون: Reem Ali (9913494) (author), Dindial Ramotar (208416) (author)
منشور في: 2023
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author Abdallah Alhaj Sulaiman (17777421)
author2 Reem Ali (9913494)
Dindial Ramotar (208416)
author2_role author
author
author_facet Abdallah Alhaj Sulaiman (17777421)
Reem Ali (9913494)
Dindial Ramotar (208416)
author_role author
dc.creator.none.fl_str_mv Abdallah Alhaj Sulaiman (17777421)
Reem Ali (9913494)
Dindial Ramotar (208416)
dc.date.none.fl_str_mv 2023-06-22T03:00:00Z
dc.identifier.none.fl_str_mv 10.1038/s41598-023-37339-y
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/The_histone_H2B_Arg95_residue_efficiently_recruits_the_transcription_factor_Spt16_to_mediate_Ste5_expression_of_the_pheromone_response_pathway/25125614
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Biochemistry and cell biology
Genetics
Rapamycin
Sirolimus
Immunosuppressant
TORC1 (Target of Rapamycin Complex 1)
Saccharomyces cerevisiae
Peptidyl-prolyl isomerase Fpr1
Cell cycle progression
Transcriptional activation
STE5 gene
Nucleosomal changes
Spot test analysis
Mass spectrometry
Chromatin structure
Gene expression
Cell cycle regulation
Phosphorylation
Protein-protein interaction
Epigenetic modification
Translational initiation factors
Nucleosome stability
dc.title.none.fl_str_mv The histone H2B Arg95 residue efficiently recruits the transcription factor Spt16 to mediate Ste5 expression of the pheromone response pathway
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">In yeast Saccharomyces cerevisiae, the immunosuppressant rapamycin inhibits the TORC1 kinase causing rapid alteration in gene expression and leading to G1 arrest. We recently reported the isolation and characterization from the histone mutant collection of a histone H2B R95A mutant that displays resistance to rapamycin. This mutant is defective in the expression of several genes belonging to the pheromone response pathway including STE5 encoding a scaffold protein that promotes the activation of downstream MAP kinases. Cells lacking Ste5 cannot arrest the cell cycle in response to rapamycin and as a consequence exhibit similar resistance to rapamycin as the H2B R95A mutant. Herein, we show that the H2B R95A mutation weakens the association of H2B with Spt16 a component of the FACT complex (FAcilitates Chromatin Transcription), and an essential factor that interacts with the histone H2A-H2B dimer to promote transcription and preserve chromatin integrity. From a collection of spt16 mutants, spt16 E857K and spt16-11 showed striking sensitivity to rapamycin as compared to the parent strain. spt16 E857K and spt16-11 expressed distinct forms of Ste5, while a suppressor mutation H2B A84D of the spt16-11 mutant prevents the expression of Ste5 and confers marked resistance to rapamycin. We interpret these findings to suggest that the Arg95 residue of histone H2B is required to recruit Spt16 to maintain the expression of STE5, which performs a role to arrest cells in the G1 phase in response to rapamycin.</p><h2>Other Information</h2><p dir="ltr">Published in: Scientific Reports<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-023-37339-y" target="_blank">https://dx.doi.org/10.1038/s41598-023-37339-y</a></p>
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network_acronym_str Manara2
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spelling The histone H2B Arg95 residue efficiently recruits the transcription factor Spt16 to mediate Ste5 expression of the pheromone response pathwayAbdallah Alhaj Sulaiman (17777421)Reem Ali (9913494)Dindial Ramotar (208416)Biological sciencesBiochemistry and cell biologyGeneticsRapamycinSirolimusImmunosuppressantTORC1 (Target of Rapamycin Complex 1)Saccharomyces cerevisiaePeptidyl-prolyl isomerase Fpr1Cell cycle progressionTranscriptional activationSTE5 geneNucleosomal changesSpot test analysisMass spectrometryChromatin structureGene expressionCell cycle regulationPhosphorylationProtein-protein interactionEpigenetic modificationTranslational initiation factorsNucleosome stability<p dir="ltr">In yeast Saccharomyces cerevisiae, the immunosuppressant rapamycin inhibits the TORC1 kinase causing rapid alteration in gene expression and leading to G1 arrest. We recently reported the isolation and characterization from the histone mutant collection of a histone H2B R95A mutant that displays resistance to rapamycin. This mutant is defective in the expression of several genes belonging to the pheromone response pathway including STE5 encoding a scaffold protein that promotes the activation of downstream MAP kinases. Cells lacking Ste5 cannot arrest the cell cycle in response to rapamycin and as a consequence exhibit similar resistance to rapamycin as the H2B R95A mutant. Herein, we show that the H2B R95A mutation weakens the association of H2B with Spt16 a component of the FACT complex (FAcilitates Chromatin Transcription), and an essential factor that interacts with the histone H2A-H2B dimer to promote transcription and preserve chromatin integrity. From a collection of spt16 mutants, spt16 E857K and spt16-11 showed striking sensitivity to rapamycin as compared to the parent strain. spt16 E857K and spt16-11 expressed distinct forms of Ste5, while a suppressor mutation H2B A84D of the spt16-11 mutant prevents the expression of Ste5 and confers marked resistance to rapamycin. We interpret these findings to suggest that the Arg95 residue of histone H2B is required to recruit Spt16 to maintain the expression of STE5, which performs a role to arrest cells in the G1 phase in response to rapamycin.</p><h2>Other Information</h2><p dir="ltr">Published in: Scientific Reports<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-023-37339-y" target="_blank">https://dx.doi.org/10.1038/s41598-023-37339-y</a></p>2023-06-22T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41598-023-37339-yhttps://figshare.com/articles/journal_contribution/The_histone_H2B_Arg95_residue_efficiently_recruits_the_transcription_factor_Spt16_to_mediate_Ste5_expression_of_the_pheromone_response_pathway/25125614CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/251256142023-06-22T03:00:00Z
spellingShingle The histone H2B Arg95 residue efficiently recruits the transcription factor Spt16 to mediate Ste5 expression of the pheromone response pathway
Abdallah Alhaj Sulaiman (17777421)
Biological sciences
Biochemistry and cell biology
Genetics
Rapamycin
Sirolimus
Immunosuppressant
TORC1 (Target of Rapamycin Complex 1)
Saccharomyces cerevisiae
Peptidyl-prolyl isomerase Fpr1
Cell cycle progression
Transcriptional activation
STE5 gene
Nucleosomal changes
Spot test analysis
Mass spectrometry
Chromatin structure
Gene expression
Cell cycle regulation
Phosphorylation
Protein-protein interaction
Epigenetic modification
Translational initiation factors
Nucleosome stability
status_str publishedVersion
title The histone H2B Arg95 residue efficiently recruits the transcription factor Spt16 to mediate Ste5 expression of the pheromone response pathway
title_full The histone H2B Arg95 residue efficiently recruits the transcription factor Spt16 to mediate Ste5 expression of the pheromone response pathway
title_fullStr The histone H2B Arg95 residue efficiently recruits the transcription factor Spt16 to mediate Ste5 expression of the pheromone response pathway
title_full_unstemmed The histone H2B Arg95 residue efficiently recruits the transcription factor Spt16 to mediate Ste5 expression of the pheromone response pathway
title_short The histone H2B Arg95 residue efficiently recruits the transcription factor Spt16 to mediate Ste5 expression of the pheromone response pathway
title_sort The histone H2B Arg95 residue efficiently recruits the transcription factor Spt16 to mediate Ste5 expression of the pheromone response pathway
topic Biological sciences
Biochemistry and cell biology
Genetics
Rapamycin
Sirolimus
Immunosuppressant
TORC1 (Target of Rapamycin Complex 1)
Saccharomyces cerevisiae
Peptidyl-prolyl isomerase Fpr1
Cell cycle progression
Transcriptional activation
STE5 gene
Nucleosomal changes
Spot test analysis
Mass spectrometry
Chromatin structure
Gene expression
Cell cycle regulation
Phosphorylation
Protein-protein interaction
Epigenetic modification
Translational initiation factors
Nucleosome stability