Gadd45a is a heterochromatin relaxer that enhances iPS cell generation.
EMBO Rep
; 17(11): 1641-1656, 2016 11.
Article
en En
| MEDLINE
| ID: mdl-27702986
ABSTRACT
Reprogramming of somatic cells to induced pluripotent stem cells rewrites the code of cell fate at the chromatin level. Yet, little is known about this process physically. Here, we describe a fluorescence recovery after photobleaching method to assess the dynamics of heterochromatin/euchromatin and show significant heterochromatin loosening at the initial stage of reprogramming. We identify growth arrest and DNA damage-inducible protein a (Gadd45a) as a chromatin relaxer in mouse embryonic fibroblasts, which also enhances somatic cell reprogramming efficiency. We show that residue glycine 39 (G39) in Gadd45a is essential for interacting with core histones, opening chromatin and enhancing reprogramming. We further demonstrate that Gadd45a destabilizes histone-DNA interactions and facilitates the binding of Yamanaka factors to their targets for activation. Our study provides a method to screen factors that impact on chromatin structure in live cells, and identifies Gadd45a as a chromatin relaxer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
/
Heterocromatina
/
Proteínas de Ciclo Celular
/
Reprogramación Celular
/
Células Madre Pluripotentes Inducidas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
EMBO Rep
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2016
Tipo del documento:
Article
País de afiliación:
China