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La cooperatividad del factor de transcripción guiado por el ADN forma la cara y el mesénquima de las extremidades
Seungsoo Kim1, Ekaterina Morgunova2, Sahin Naqvi3
1Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford, CA 94305, USA.
Cell
|January 23, 2024
Resumen
Un nuevo motivo de ADN, "Coordinador", permite la cooperación de factores de transcripción, especificando las identidades celulares de la cara y las extremidades embrionarias. Este mecanismo, que involucra a los factores TWIST1 y homeodomain, regula los genes cruciales para la morfología y la evolución.
Área de la Ciencia:
- Biología del desarrollo
- Biología molecular
- La genética
Sus antecedentes:
- Los factores de transcripción (TF) establecen la identidad celular, pero los mecanismos de especificidad con sitios de unión al ADN similares no están claros.
- La cooperatividad TF guiada por ADN es un mecanismo propuesto, sin embargo, los ejemplos in vivo son limitados.
Objetivo del estudio:
- Identificar y caracterizar un motivo de ADN que confiere especificidad reguladora en el desarrollo embrionario.
- Para aclarar el mecanismo de unión cooperativa entre TWIST1 y el homeodomain (HD) TFs en este motivo.
Principales métodos:
- Identificación del motivo de ADN "coordinador" en las regiones reguladoras del mesénquima de la cara y las extremidades embrionarias.
- Análisis de la dinámica de unión de los factores TWIST1 y HD en los sitios coordinadores.
- Evaluación de la accesibilidad de la cromatina y la regulación génica influenciadas por esta unión cooperativa.
Principales resultados:
- El motivo "Coordinador" recluta selectivamente los factores TWIST1 y HD para la vinculación cooperativa.
- TWIST1 es esencial para la unión del factor HD y la apertura de la cromatina en los sitios coordinadores.
- Los factores de la EH estabilizan la unión de TWIST1 y regulan la expresión génica objetivo involucrada en la identidad y la morfología celular.
Conclusiones:
- La cooperatividad TF guiada por el ADN, mediada por el motivo "Coordinador", es un mecanismo clave para establecer identidades celulares distintas en el desarrollo embrionario.
- Este mecanismo juega un papel importante en la configuración de la morfología facial y los procesos evolutivos.
Palabras clave:
Factores de ALXEl coordinadorTWIST1 (en inglés)bLH yla cooperatividadel rostroDominio de origenel miembroMezénquimala cresta neuronalFactor de transcripciónMás Videos Relacionados
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