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Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity.
Park, Jeehae; Estrada, Javier; Johnson, Gemma; Vincent, Ben J; Ricci-Tam, Chiara; Bragdon, Meghan Dj; Shulgina, Yekaterina; Cha, Anna; Wunderlich, Zeba; Gunawardena, Jeremy; DePace, Angela H.
Afiliación
  • Park J; Department of Systems Biology, Harvard Medical School, Boston, United States.
  • Estrada J; Department of Systems Biology, Harvard Medical School, Boston, United States.
  • Johnson G; Department of Systems Biology, Harvard Medical School, Boston, United States.
  • Vincent BJ; Department of Systems Biology, Harvard Medical School, Boston, United States.
  • Ricci-Tam C; Department of Systems Biology, Harvard Medical School, Boston, United States.
  • Bragdon MD; Department of Systems Biology, Harvard Medical School, Boston, United States.
  • Shulgina Y; Department of Systems Biology, Harvard Medical School, Boston, United States.
  • Cha A; Department of Systems Biology, Harvard Medical School, Boston, United States.
  • Wunderlich Z; Department of Systems Biology, Harvard Medical School, Boston, United States.
  • Gunawardena J; Department of Systems Biology, Harvard Medical School, Boston, United States.
  • DePace AH; Department of Systems Biology, Harvard Medical School, Boston, United States.
Elife ; 82019 06 21.
Article en En | MEDLINE | ID: mdl-31223115
Developmental enhancers integrate graded concentrations of transcription factors (TFs) to create sharp gene expression boundaries. Here we examine the hunchback P2 (HbP2) enhancer which drives a sharp expression pattern in the Drosophila blastoderm embryo in response to the transcriptional activator Bicoid (Bcd). We systematically interrogate cis and trans factors that influence the shape and position of expression driven by HbP2, and find that the prevailing model, based on pairwise cooperative binding of Bcd to HbP2 is not adequate. We demonstrate that other proteins, such as pioneer factors, Mediator and histone modifiers influence the shape and position of the HbP2 expression pattern. Comparing our results to theory reveals how higher-order cooperativity and energy expenditure impact boundary location and sharpness. Our results emphasize that the bacterial view of transcription regulation, where pairwise interactions between regulatory proteins dominate, must be reexamined in animals, where multiple molecular mechanisms collaborate to shape the gene regulatory function.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Transactivadores / Proteínas de Homeodominio / Regulación del Desarrollo de la Expresión Génica / Proteínas de Drosophila / Proteínas de Unión al ADN / Drosophila Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Elife Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Transactivadores / Proteínas de Homeodominio / Regulación del Desarrollo de la Expresión Génica / Proteínas de Drosophila / Proteínas de Unión al ADN / Drosophila Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Elife Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido