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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/228409
Ver los metadatos del registro completo
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CONICET Digital (CONICET) |
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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 Técnicas2025-09-03T09:51:11Zoai: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:34982025-09-03 09:51:11.303CONICET 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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13.13397 |