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Genetic dissection of the α-globin super-enhancer in vivo.
Hay, Deborah; Hughes, Jim R; Babbs, Christian; Davies, James O J; Graham, Bryony J; Hanssen, Lars; Kassouf, Mira T; Marieke Oudelaar, A Marieke; Sharpe, Jacqueline A; Suciu, Maria C; Telenius, Jelena; Williams, Ruth; Rode, Christina; Li, Pik-Shan; Pennacchio, Len A; Sloane-Stanley, Jacqueline A; Ayyub, Helena; Butler, Sue; Sauka-Spengler, Tatjana; Gibbons, Richard J; Smith, Andrew J H; Wood, William G; Higgs, Douglas R.
Afiliación
  • Hay D; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Hughes JR; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Babbs C; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Davies JOJ; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Graham BJ; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Hanssen L; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Kassouf MT; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Marieke Oudelaar AM; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Sharpe JA; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Suciu MC; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Telenius J; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Williams R; Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Rode C; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Li PS; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Pennacchio LA; Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California.
  • Sloane-Stanley JA; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Ayyub H; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Butler S; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Sauka-Spengler T; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Gibbons RJ; Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Smith AJH; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Wood WG; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
  • Higgs DR; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, UK.
Nat Genet ; 48(8): 895-903, 2016 08.
Article en En | MEDLINE | ID: mdl-27376235
Many genes determining cell identity are regulated by clusters of Mediator-bound enhancer elements collectively referred to as super-enhancers. These super-enhancers have been proposed to manifest higher-order properties important in development and disease. Here we report a comprehensive functional dissection of one of the strongest putative super-enhancers in erythroid cells. By generating a series of mouse models, deleting each of the five regulatory elements of the α-globin super-enhancer individually and in informative combinations, we demonstrate that each constituent enhancer seems to act independently and in an additive fashion with respect to hematological phenotype, gene expression, chromatin structure and chromosome conformation, without clear evidence of synergistic or higher-order effects. Our study highlights the importance of functional genetic analyses for the identification of new concepts in transcriptional regulation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Transcripción Genética / Regulación de la Expresión Génica / Elementos de Facilitación Genéticos / Células Eritroides / Globinas alfa Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Transcripción Genética / Regulación de la Expresión Génica / Elementos de Facilitación Genéticos / Células Eritroides / Globinas alfa Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos