期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 431, 期 6, 页码 1148-1159出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2019.02.012
关键词
pluripotency transcription factors; neural progenitors; super-enhancer; fluorescence correlation spectroscopy; CRISPR/Cas9
资金
- Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET)
- Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCyT) [PICT 2011-2713, PIP112-201101-00243, PID-2014-0052]
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. (C) 2019 Elsevier Ltd. All rights reserved.
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