Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation

Publication date: Available online 18 February 2019Source: Journal of Molecular BiologyAuthor(s): María Soledad Cosentino, Camila Oses, Camila Vázquez Echegaray, Claudia Solari, Ariel Waisman, Yanina Álvarez, María Victoria Petrone, Marcos Francia, Marcelo Schultz, Gustavo Sevlever, Santiago Miriuka, Valeria Levi, Alejandra GubermanAbstractChromatin 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 (TFs) 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 plasticit...
Source: Journal of Molecular Biology - Category: Molecular Biology Source Type: research