GATA Factor-Regulated Samd14 Enhancer Confers Red Blood Cell Regeneration and Survival in Severe Anemia.
Dev Cell
; 42(3): 213-225.e4, 2017 08 07.
Article
en En
| MEDLINE
| ID: mdl-28787589
ABSTRACT
An enhancer with amalgamated E-box and GATA motifs (+9.5) controls expression of the regulator of hematopoiesis GATA-2. While similar GATA-2-occupied elements are common in the genome, occupancy does not predict function, and GATA-2-dependent genetic networks are incompletely defined. A "+9.5-like" element resides in an intron of Samd14 (Samd14-Enh) encoding a sterile alpha motif (SAM) domain protein. Deletion of Samd14-Enh in mice strongly decreased Samd14 expression in bone marrow and spleen. Although steady-state hematopoiesis was normal, Samd14-Enh-/- mice died in response to severe anemia. Samd14-Enh stimulated stem cell factor/c-Kit signaling, which promotes erythrocyte regeneration. Anemia activated Samd14-Enh by inducing enhancer components and enhancer chromatin accessibility. Thus, a GATA-2/anemia-regulated enhancer controls expression of an SAM domain protein that confers survival in anemia. We propose that Samd14-Enh and an ensemble of anemia-responsive enhancers are essential for erythrocyte regeneration in stress erythropoiesis, a vital process in pathologies, including ß-thalassemia, myelodysplastic syndrome, and viral infection.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas
/
Elementos de Facilitación Genéticos
/
Eritrocitos
/
Eritropoyesis
/
Factores de Transcripción GATA
/
Anemia
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Dev Cell
Asunto de la revista:
EMBRIOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos