Dynamic switching of transcriptional regulators between two distinct low-mobility chromatin states

Autores
Wagh, Kaustubh; Stavreva, Diana A.; Jensen, Rikke A.M.; Paakinaho, Ville; Fettweis, Gregory; Schiltz, R. Louis; Wüstner, Daniel; Mandrup, Susanne; Presman, Diego Martin; Upadhyaya, Arpita; Hager, Gordon L.
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
How chromatin dynamics relate to transcriptional activity remains poorly understood. Using single-molecule tracking, coupled with machine learning, we show that histone H2B and multiple chromatin-bound transcriptional regulators display two distinct low-mobility states. Ligand activation results in a marked increase in the propensity of steroid receptors to bind in the lowest-mobility state. Mutational analysis revealed that interactions with chromatin in the lowest-mobility state require an intact DNA binding domain and oligomerization domains. These states are not spatially separated as previously believed, but individual H2B and bound-TF molecules can dynamically switch between them on time scales of seconds. Single bound-TF molecules with different mobilities exhibit different dwell time distributions, suggesting that the mobility of TFs is intimately coupled with their binding dynamics. Together, our results identify two unique and distinct low-mobility states that appear to represent common pathways for transcription activation in mammalian cells.
Fil: Wagh, Kaustubh. National Institutes of Health; Estados Unidos. University of Maryland; Estados Unidos
Fil: Stavreva, Diana A.. National Institutes of Health; Estados Unidos
Fil: Jensen, Rikke A.M.. University Of Southern Denmark; Dinamarca. National Institutes of Health; Estados Unidos
Fil: Paakinaho, Ville. University Of Eastern Finland.; Finlandia. National Institutes of Health; Estados Unidos
Fil: Fettweis, Gregory. National Institutes of Health; Estados Unidos
Fil: Schiltz, R. Louis. National Institutes of Health; Estados Unidos
Fil: Wüstner, Daniel. University Of Southern Denmark; Dinamarca
Fil: Mandrup, Susanne. University Of Southern Denmark; Dinamarca
Fil: Presman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. National Institutes of Health; Estados Unidos
Fil: Upadhyaya, Arpita. University of Maryland; Estados Unidos
Fil: Hager, Gordon L.. National Institutes of Health; Estados Unidos
Materia
CHROMATIN DYNAMICS
SINGLE-MOLECULE
GLUCOCORTICOID RECEPTOR
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/228409
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/228409
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Dynamic switching of transcriptional regulators between two distinct low-mobility chromatin statesWagh, KaustubhStavreva, Diana A.Jensen, Rikke A.M.Paakinaho, VilleFettweis, GregorySchiltz, R. LouisWüstner, DanielMandrup, SusannePresman, Diego MartinUpadhyaya, ArpitaHager, Gordon L.CHROMATIN DYNAMICSSINGLE-MOLECULEGLUCOCORTICOID RECEPTORhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1How chromatin dynamics relate to transcriptional activity remains poorly understood. Using single-molecule tracking, coupled with machine learning, we show that histone H2B and multiple chromatin-bound transcriptional regulators display two distinct low-mobility states. Ligand activation results in a marked increase in the propensity of steroid receptors to bind in the lowest-mobility state. Mutational analysis revealed that interactions with chromatin in the lowest-mobility state require an intact DNA binding domain and oligomerization domains. These states are not spatially separated as previously believed, but individual H2B and bound-TF molecules can dynamically switch between them on time scales of seconds. Single bound-TF molecules with different mobilities exhibit different dwell time distributions, suggesting that the mobility of TFs is intimately coupled with their binding dynamics. Together, our results identify two unique and distinct low-mobility states that appear to represent common pathways for transcription activation in mammalian cells.Fil: Wagh, Kaustubh. National Institutes of Health; Estados Unidos. University of Maryland; Estados UnidosFil: Stavreva, Diana A.. National Institutes of Health; Estados UnidosFil: Jensen, Rikke A.M.. University Of Southern Denmark; Dinamarca. National Institutes of Health; Estados UnidosFil: Paakinaho, Ville. University Of Eastern Finland.; Finlandia. National Institutes of Health; Estados UnidosFil: Fettweis, Gregory. National Institutes of Health; Estados UnidosFil: Schiltz, R. Louis. National Institutes of Health; Estados UnidosFil: Wüstner, Daniel. University Of Southern Denmark; DinamarcaFil: Mandrup, Susanne. University Of Southern Denmark; DinamarcaFil: Presman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. National Institutes of Health; Estados UnidosFil: Upadhyaya, Arpita. University of Maryland; Estados UnidosFil: Hager, Gordon L.. National Institutes of Health; Estados UnidosScience Advances is the American Association for the Advancement of Science2023-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/228409Wagh, Kaustubh; Stavreva, Diana A.; Jensen, Rikke A.M.; Paakinaho, Ville; Fettweis, Gregory; et al.; Dynamic switching of transcriptional regulators between two distinct low-mobility chromatin states; Science Advances is the American Association for the Advancement of Science; Science Advances; 9; 24; 6-2023; 1-202375-2548CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.science.org/doi/10.1126/sciadv.ade1122info:eu-repo/semantics/altIdentifier/doi/10.1126/sciadv.ade1122info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:47:06Zoai:ri.conicet.gov.ar:11336/228409instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:47:07.042CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Dynamic switching of transcriptional regulators between two distinct low-mobility chromatin states
title Dynamic switching of transcriptional regulators between two distinct low-mobility chromatin states
spellingShingle Dynamic switching of transcriptional regulators between two distinct low-mobility chromatin states
Wagh, Kaustubh
CHROMATIN DYNAMICS
SINGLE-MOLECULE
GLUCOCORTICOID RECEPTOR
title_short Dynamic switching of transcriptional regulators between two distinct low-mobility chromatin states
title_full Dynamic switching of transcriptional regulators between two distinct low-mobility chromatin states
title_fullStr Dynamic switching of transcriptional regulators between two distinct low-mobility chromatin states
title_full_unstemmed Dynamic switching of transcriptional regulators between two distinct low-mobility chromatin states
title_sort Dynamic switching of transcriptional regulators between two distinct low-mobility chromatin states
dc.creator.none.fl_str_mv Wagh, Kaustubh
Stavreva, Diana A.
Jensen, Rikke A.M.
Paakinaho, Ville
Fettweis, Gregory
Schiltz, R. Louis
Wüstner, Daniel
Mandrup, Susanne
Presman, Diego Martin
Upadhyaya, Arpita
Hager, Gordon L.
author Wagh, Kaustubh
author_facet Wagh, Kaustubh
Stavreva, Diana A.
Jensen, Rikke A.M.
Paakinaho, Ville
Fettweis, Gregory
Schiltz, R. Louis
Wüstner, Daniel
Mandrup, Susanne
Presman, Diego Martin
Upadhyaya, Arpita
Hager, Gordon L.
author_role author
author2 Stavreva, Diana A.
Jensen, Rikke A.M.
Paakinaho, Ville
Fettweis, Gregory
Schiltz, R. Louis
Wüstner, Daniel
Mandrup, Susanne
Presman, Diego Martin
Upadhyaya, Arpita
Hager, Gordon L.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CHROMATIN DYNAMICS
SINGLE-MOLECULE
GLUCOCORTICOID RECEPTOR
topic CHROMATIN DYNAMICS
SINGLE-MOLECULE
GLUCOCORTICOID RECEPTOR
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv How chromatin dynamics relate to transcriptional activity remains poorly understood. Using single-molecule tracking, coupled with machine learning, we show that histone H2B and multiple chromatin-bound transcriptional regulators display two distinct low-mobility states. Ligand activation results in a marked increase in the propensity of steroid receptors to bind in the lowest-mobility state. Mutational analysis revealed that interactions with chromatin in the lowest-mobility state require an intact DNA binding domain and oligomerization domains. These states are not spatially separated as previously believed, but individual H2B and bound-TF molecules can dynamically switch between them on time scales of seconds. Single bound-TF molecules with different mobilities exhibit different dwell time distributions, suggesting that the mobility of TFs is intimately coupled with their binding dynamics. Together, our results identify two unique and distinct low-mobility states that appear to represent common pathways for transcription activation in mammalian cells.
Fil: Wagh, Kaustubh. National Institutes of Health; Estados Unidos. University of Maryland; Estados Unidos
Fil: Stavreva, Diana A.. National Institutes of Health; Estados Unidos
Fil: Jensen, Rikke A.M.. University Of Southern Denmark; Dinamarca. National Institutes of Health; Estados Unidos
Fil: Paakinaho, Ville. University Of Eastern Finland.; Finlandia. National Institutes of Health; Estados Unidos
Fil: Fettweis, Gregory. National Institutes of Health; Estados Unidos
Fil: Schiltz, R. Louis. National Institutes of Health; Estados Unidos
Fil: Wüstner, Daniel. University Of Southern Denmark; Dinamarca
Fil: Mandrup, Susanne. University Of Southern Denmark; Dinamarca
Fil: Presman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. National Institutes of Health; Estados Unidos
Fil: Upadhyaya, Arpita. University of Maryland; Estados Unidos
Fil: Hager, Gordon L.. National Institutes of Health; Estados Unidos
description How chromatin dynamics relate to transcriptional activity remains poorly understood. Using single-molecule tracking, coupled with machine learning, we show that histone H2B and multiple chromatin-bound transcriptional regulators display two distinct low-mobility states. Ligand activation results in a marked increase in the propensity of steroid receptors to bind in the lowest-mobility state. Mutational analysis revealed that interactions with chromatin in the lowest-mobility state require an intact DNA binding domain and oligomerization domains. These states are not spatially separated as previously believed, but individual H2B and bound-TF molecules can dynamically switch between them on time scales of seconds. Single bound-TF molecules with different mobilities exhibit different dwell time distributions, suggesting that the mobility of TFs is intimately coupled with their binding dynamics. Together, our results identify two unique and distinct low-mobility states that appear to represent common pathways for transcription activation in mammalian cells.
publishDate 2023
dc.date.none.fl_str_mv 2023-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/228409
Wagh, Kaustubh; Stavreva, Diana A.; Jensen, Rikke A.M.; Paakinaho, Ville; Fettweis, Gregory; et al.; Dynamic switching of transcriptional regulators between two distinct low-mobility chromatin states; Science Advances is the American Association for the Advancement of Science; Science Advances; 9; 24; 6-2023; 1-20
2375-2548
CONICET Digital
CONICET
url http://hdl.handle.net/11336/228409
identifier_str_mv Wagh, Kaustubh; Stavreva, Diana A.; Jensen, Rikke A.M.; Paakinaho, Ville; Fettweis, Gregory; et al.; Dynamic switching of transcriptional regulators between two distinct low-mobility chromatin states; Science Advances is the American Association for the Advancement of Science; Science Advances; 9; 24; 6-2023; 1-20
2375-2548
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.science.org/doi/10.1126/sciadv.ade1122
info:eu-repo/semantics/altIdentifier/doi/10.1126/sciadv.ade1122
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Science Advances is the American Association for the Advancement of Science
publisher.none.fl_str_mv Science Advances is the American Association for the Advancement of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.069144

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