Cosentino, M.S.; Oses, C.; Vázquez Echegaray, C.; Solari, C.; Waisman, A.; Álvarez, Y.; Petrone, M.V.; Francia, M.; Schultz, M.; Sevlever, G.; Miriuka, S.; Levi, V.; Guberman, A. "Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation" (2019) Journal of Molecular Biology. 431(6):1148-1159
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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. © 2019 Elsevier Ltd


Documento: Artículo
Título:Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation
Autor:Cosentino, M.S.; Oses, C.; Vázquez Echegaray, C.; Solari, C.; Waisman, A.; Álvarez, Y.; Petrone, M.V.; Francia, M.; Schultz, M.; Sevlever, G.; Miriuka, S.; Levi, V.; Guberman, A.
Filiación:Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Buenos Aires, Argentina
CONICET—Universidad de Buenos Aires, Instituto de Química Biológica (IQUIBICEN), Buenos Aires, Argentina
CONICET—Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Laboratorio de Investigación de Aplicación a Neurociencias (LIAN), Buenos Aires, Argentina
Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Fisiología y Biología Molecular y Celular, Buenos Aires, Argentina
Established investigators from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Palabras clave:CRISPR/Cas9; fluorescence correlation spectroscopy; neural progenitors; pluripotency transcription factors; super-enhancer; CRISPR associated endonuclease Cas9; heterochromatin protein 1; heterochromatin protein 1 alpha; histone acetyltransferase; histone acetyltransferase Kat6b; Ki 67 antigen; messenger RNA; octamer transcription factor 4; short hairpin RNA; transcription factor NANOG; transcription factor Sox2; unclassified drug; animal cell; animal experiment; Article; cell fate; cell lineage; cell proliferation; cell structure; cell viability; cellular distribution; chromatin; chromatin assembly and disassembly; controlled study; CRISPR-CAS9 system; embryo; embryonic stem cell; epigenetics; fluorescence correlation spectroscopy; gene expression; gene knockout; genetic transcription; immunochemistry; Kat6b gene; male; molecular dynamics; mouse; nerve cell differentiation; nerve cell plasticity; neural stem cell; neuromodulation; nonhuman; priority journal; protein analysis; protein binding; protein expression; protein function; protein protein interaction; RNA sequence; stem cell self-renewal
Página de inicio:1148
Página de fin:1159
Título revista:Journal of Molecular Biology
Título revista abreviado:J. Mol. Biol.
CAS:CRISPR associated endonuclease Cas9; esterase; histone acetyltransferase, 9054-51-7; histone acetyltransferase KAT5


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---------- APA ----------
Cosentino, M.S., Oses, C., Vázquez Echegaray, C., Solari, C., Waisman, A., Álvarez, Y., Petrone, M.V.,..., Guberman, A. (2019) . Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation. Journal of Molecular Biology, 431(6), 1148-1159.
---------- CHICAGO ----------
Cosentino, M.S., Oses, C., Vázquez Echegaray, C., Solari, C., Waisman, A., Álvarez, Y., et al. "Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation" . Journal of Molecular Biology 431, no. 6 (2019) : 1148-1159.
---------- MLA ----------
Cosentino, M.S., Oses, C., Vázquez Echegaray, C., Solari, C., Waisman, A., Álvarez, Y., et al. "Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation" . Journal of Molecular Biology, vol. 431, no. 6, 2019, pp. 1148-1159.
---------- VANCOUVER ----------
Cosentino, M.S., Oses, C., Vázquez Echegaray, C., Solari, C., Waisman, A., Álvarez, Y., et al. Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation. J. Mol. Biol. 2019;431(6):1148-1159.