info:eu-repo/semantics/article
Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation
Fecha
2019-03Registro en:
Cosentino, María Soledad; Oses Oliveto, Camila Maite; Echegaray, Camila Vázquez; Solari, Claudia María; Waisman, Ariel; et al.; Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation; Academic Press Ltd - Elsevier Science Ltd; Journal Of Molecular Biology; 431; 6; 3-2019; 1148-1159
0022-2836
CONICET Digital
CONICET
Autor
Cosentino, María Soledad
Oses Oliveto, Camila Maite
Echegaray, Camila Vázquez
Solari, Claudia María
Waisman, Ariel
Álvarez, Yanina
Petrone Parcero, María Victoria
Francia, Marcos Gabriel
Schultz, Marcelo
Sevlever, Gustavo
Miriuka, Santiago Gabriel
Levi, Valeria
Guberman, Alejandra Sonia
Resumen
Chromatin remodeling is fundamental for the dynamical changes in transcriptional programs that occur during development and stem cell differentiation. The histone acetyltransferase Kat6b is relevant for neurogenesis in mouse embryos, and mutations of this gene cause intellectual disability in humans. However, the molecular mechanisms involved in Kat6b mutant phenotype and the role of this chromatin modifier in embryonic stem (ES) cells remain elusive. In this work, we show that Kat6b is expressed in ES cells and is repressed during differentiation. Moreover, we found that this gene is regulated by the pluripotency transcription factors Nanog and Oct4. To study the functional relevance of Kat6b in ES cells, we generated a Kat6b knockout ES cell line (K6b −/−) using CRISPR/Cas9. Fluorescence correlation spectroscopy analyses suggest a more compact chromatin organization in K6b −/− cells and impaired interactions of Oct4 and Nanog with chromatin. Remarkably, K6b −/− cells showed a reduced efficiency to differentiate to neural lineage. These results reveal a role of Kat6b as a modulator of chromatin plasticity, its impact on chromatin-transcription factors interactions and its influence on cell fate decisions during neural development.