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Artículo

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

Wagh, Kaustubh; Stavreva, Diana A.; Jensen, Rikke A.M.; Paakinaho, Ville; Fettweis, Gregory; Schiltz, R. Louis; Wüstner, Daniel; Mandrup, Susanne; Presman, Diego MartinIcon ; Upadhyaya, Arpita; Hager, Gordon L.
Fecha de publicación: 06/2023
Editorial: Science Advances is the American Association for the Advancement of Science
Revista: Science Advances
e-ISSN: 2375-2548
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Biofísica

Resumen

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.
Palabras clave: CHROMATIN DYNAMICS , SINGLE-MOLECULE , GLUCOCORTICOID RECEPTOR
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution 2.5 Unported (CC BY 2.5)
Identificadores
URI: http://hdl.handle.net/11336/228409
URL: https://www.science.org/doi/10.1126/sciadv.ade1122
DOI: http://dx.doi.org/10.1126/sciadv.ade1122
Colecciones
Articulos(IFIBYNE)
Articulos de INST.DE FISIOL., BIOL.MOLECULAR Y NEUROCIENCIAS
Citación
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
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