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Enforcement of developmental lineage specificity by transcription factor Oct1.
Shen, Zuolian; Kang, Jinsuk; Shakya, Arvind; Tabaka, Marcin; Jarboe, Elke A; Regev, Aviv; Tantin, Dean.
Afiliación
  • Shen Z; Department of Pathology, University of Utah School of Medicine, Salt Lake City, United States.
  • Kang J; Department of Pathology, University of Utah School of Medicine, Salt Lake City, United States.
  • Shakya A; Department of Pathology, University of Utah School of Medicine, Salt Lake City, United States.
  • Tabaka M; The Broad Institute of MIT and Harvard, Cambridge, United States.
  • Jarboe EA; Department of Pathology, University of Utah School of Medicine, Salt Lake City, United States.
  • Regev A; The Broad Institute of MIT and Harvard, Cambridge, United States.
  • Tantin D; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, United States.
Elife ; 62017 05 24.
Article en En | MEDLINE | ID: mdl-28537559
Embryonic stem cells co-express Oct4 and Oct1, a related protein with similar DNA-binding specificity. To study the role of Oct1 in ESC pluripotency and transcriptional control, we constructed germline and inducible-conditional Oct1-deficient ESC lines. ESCs lacking Oct1 show normal appearance, self-renewal and growth but manifest defects upon differentiation. They fail to form beating cardiomyocytes, generate neurons poorly, form small, poorly differentiated teratomas, and cannot generate chimeric mice. Upon RA-mediated differentiation, Oct1-deficient cells induce lineage-appropriate developmentally poised genes poorly while lineage-inappropriate genes, including extra-embryonic genes, are aberrantly expressed. In ESCs, Oct1 co-occupies a specific set of targets with Oct4, but does not occupy differentially expressed developmental targets. Instead, Oct1 occupies these targets as cells differentiate and Oct4 declines. These results identify a dynamic interplay between Oct1 and Oct4, in particular during the critical window immediately after loss of pluripotency when cells make the earliest developmental fate decisions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transcripción Genética / Diferenciación Celular / Regulación del Desarrollo de la Expresión Génica / Factor 1 de Transcripción de Unión a Octámeros / Células Madre Embrionarias de Ratones Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Elife Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transcripción Genética / Diferenciación Celular / Regulación del Desarrollo de la Expresión Génica / Factor 1 de Transcripción de Unión a Octámeros / Células Madre Embrionarias de Ratones Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Elife Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido