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

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...

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Autor principal: Cosentino, M.S
Otros Autores: 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.
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: Academic Press 2019
Acceso en línea:Registro en Scopus
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024 7 |2 cas  |a CRISPR associated endonuclease Cas9; esterase; histone acetyltransferase, 9054-51-7; histone acetyltransferase KAT5 
040 |a Scopus  |b spa  |c AR-BaUEN  |d AR-BaUEN 
030 |a JMOBA 
100 1 |a Cosentino, M.S. 
245 1 0 |a Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation 
260 |b Academic Press  |c 2019 
270 1 0 |m Guberman, A.Argentina; email: algub@qb.fcen.uba.ar 
506 |2 openaire  |e Política editorial 
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520 3 |a 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  |l eng 
536 |a Detalles de la financiación: Agencia Nacional de Promoción Científica y Tecnológica, PICT 2011-2713, PIP112-201101-00243, PID-2014-0052 
536 |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas 
536 |a Detalles de la financiación: This work was supported by grants from Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), and Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT): PICT 2011-2713 and PIP112-201101-00243 (to A.G.) and PID-2014-0052 (to S.M.). Appendix A 
593 |a Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Buenos Aires, Argentina 
593 |a CONICET—Universidad de Buenos Aires, Instituto de Química Biológica (IQUIBICEN), Buenos Aires, Argentina 
593 |a CONICET—Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Laboratorio de Investigación de Aplicación a Neurociencias (LIAN), Buenos Aires, Argentina 
593 |a Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Fisiología y Biología Molecular y Celular, Buenos Aires, Argentina 
593 |a Established investigators from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina 
690 1 0 |a CRISPR/CAS9 
690 1 0 |a FLUORESCENCE CORRELATION SPECTROSCOPY 
690 1 0 |a NEURAL PROGENITORS 
690 1 0 |a PLURIPOTENCY TRANSCRIPTION FACTORS 
690 1 0 |a SUPER-ENHANCER 
690 1 0 |a CRISPR ASSOCIATED ENDONUCLEASE CAS9 
690 1 0 |a HETEROCHROMATIN PROTEIN 1 
690 1 0 |a HETEROCHROMATIN PROTEIN 1 ALPHA 
690 1 0 |a HISTONE ACETYLTRANSFERASE 
690 1 0 |a HISTONE ACETYLTRANSFERASE KAT6B 
690 1 0 |a KI 67 ANTIGEN 
690 1 0 |a MESSENGER RNA 
690 1 0 |a OCTAMER TRANSCRIPTION FACTOR 4 
690 1 0 |a SHORT HAIRPIN RNA 
690 1 0 |a TRANSCRIPTION FACTOR NANOG 
690 1 0 |a TRANSCRIPTION FACTOR SOX2 
690 1 0 |a UNCLASSIFIED DRUG 
690 1 0 |a ANIMAL CELL 
690 1 0 |a ANIMAL EXPERIMENT 
690 1 0 |a ARTICLE 
690 1 0 |a CELL FATE 
690 1 0 |a CELL LINEAGE 
690 1 0 |a CELL PROLIFERATION 
690 1 0 |a CELL STRUCTURE 
690 1 0 |a CELL VIABILITY 
690 1 0 |a CELLULAR DISTRIBUTION 
690 1 0 |a CHROMATIN 
690 1 0 |a CHROMATIN ASSEMBLY AND DISASSEMBLY 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a CRISPR-CAS9 SYSTEM 
690 1 0 |a EMBRYO 
690 1 0 |a EMBRYONIC STEM CELL 
690 1 0 |a EPIGENETICS 
690 1 0 |a FLUORESCENCE CORRELATION SPECTROSCOPY 
690 1 0 |a GENE EXPRESSION 
690 1 0 |a GENE KNOCKOUT 
690 1 0 |a GENETIC TRANSCRIPTION 
690 1 0 |a IMMUNOCHEMISTRY 
690 1 0 |a KAT6B GENE 
690 1 0 |a MALE 
690 1 0 |a MOLECULAR DYNAMICS 
690 1 0 |a MOUSE 
690 1 0 |a NERVE CELL DIFFERENTIATION 
690 1 0 |a NERVE CELL PLASTICITY 
690 1 0 |a NEURAL STEM CELL 
690 1 0 |a NEUROMODULATION 
690 1 0 |a NONHUMAN 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a PROTEIN ANALYSIS 
690 1 0 |a PROTEIN BINDING 
690 1 0 |a PROTEIN EXPRESSION 
690 1 0 |a PROTEIN FUNCTION 
690 1 0 |a PROTEIN PROTEIN INTERACTION 
690 1 0 |a RNA SEQUENCE 
690 1 0 |a STEM CELL SELF-RENEWAL 
700 1 |a Oses, C. 
700 1 |a Vázquez Echegaray, C. 
700 1 |a Solari, C. 
700 1 |a Waisman, A. 
700 1 |a Álvarez, Y. 
700 1 |a Petrone, M.V. 
700 1 |a Francia, M. 
700 1 |a Schultz, M. 
700 1 |a Sevlever, G. 
700 1 |a Miriuka, S. 
700 1 |a Levi, V. 
700 1 |a Guberman, A. 
773 0 |d Academic Press, 2019  |g v. 431  |h pp. 1148-1159  |k n. 6  |p J. Mol. Biol.  |x 00222836  |w (AR-BaUEN)CENRE-1757  |t Journal of Molecular Biology 
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856 4 0 |u https://doi.org/10.1016/j.jmb.2019.02.012  |y DOI 
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