SCL and associated proteins distinguish active from repressive GATA transcription factor complexes.
Blood
; 113(10): 2191-201, 2009 Mar 05.
Article
en En
| MEDLINE
| ID: mdl-19011221
ABSTRACT
GATA-1 controls hematopoietic development by activating and repressing gene transcription, yet the in vivo mechanisms that specify these opposite activities are unknown. By examining the composition of GATA-1-associated protein complexes in a conditional erythroid rescue system as well as through the use of tiling arrays we detected the SCL/TAL1, LMO2, Ldb1, E2A complex at all positively acting GATA-1-bound elements examined. Similarly, the SCL complex is present at all activating GATA elements in megakaryocytes and mast cells. In striking contrast, at sites where GATA-1 functions as a repressor, the SCL complex is depleted. A DNA-binding defective form of SCL maintains association with a subset of active GATA elements indicating that GATA-1 is a key determinant for SCL recruitment. Knockdown of LMO2 selectively impairs activation but not repression by GATA-1. ETO-2, an SCL-associated protein with the potential for transcription repression, is also absent from GATA-1-repressed genes but, unlike SCL, fails to accumulate at GATA-1-activated genes. Together, these studies identify the SCL complex as a critical and consistent determinant of positive GATA-1 activity in multiple GATA-1-regulated hematopoietic cell lineages.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Sanguíneas
/
Regulación de la Expresión Génica
/
Proteínas Proto-Oncogénicas
/
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
/
Factor de Transcripción GATA1
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Blood
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos