Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/75685
COMPARTIR / EXPORTAR:
SHARE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Tcra enhancer activation by inducible transcription factors downstream of pre-TCR signaling |
Autor: | Blanco, Beatriz del CSIC ORCID; García-Mariscal, Alberto; Wiest, David L.; Hernández-Munaín, Cristina | Fecha de publicación: | 2012 | Editor: | American Association of Immunologists | Citación: | Journal of Immunology 188: 3278- 3293 (2012) | Resumen: | The Tcra enhancer (E¿) is essential for pre-TCR-mediated activation of germline transcription and V(D)J recombination. E¿ is considered an archetypical enhanceosome that acts through the functional synergy and cooperative binding of multiple transcription factors. Based on dimethylsulfate genomic footprinting experiments, there has been a long-standing paradox regarding E¿ activation in the absence of differences in enhancer occupancy. Our data provide the molecular mechanism of E¿ activation and an explanation of this paradox. We found that germline transcriptional activation of Tcra is dependent on constant phospholipase C¿, as well as calcineurin- and MAPK/ERK-mediated signaling, indicating that inducible transcription factors are crucially involved. NFAT, AP-1, and early growth response factor 1, together with CREB-binding protein/p300 coactivators, bind to E¿ as part of an active enhanceosome assembled during pre-TCR signaling. We favor a scenario in which the binding of lymphoid-restricted and constitutive transcription factors to E¿ prior to its activation forms a regulatory scaffold to recruit factors induced by pre-TCR signaling. Thus, the combinatorial assembly of tissue- and signal-specific transcription factors dictates the E¿ function. This mechanism for enhancer activation may represent a general paradigm in tissue-restricted and stimulus-responsive gene regulation. | URI: | http://hdl.handle.net/10261/75685 | Identificadores: | issn: 0022-1767 |
Aparece en las colecciones: | (IPBLN) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
Page view(s)
287
checked on 23-abr-2024
Download(s)
86
checked on 23-abr-2024
Google ScholarTM
Check
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.