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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2019
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00222836_v431_n6_p1148_Cosentino http://hdl.handle.net/20.500.12110/paper_00222836_v431_n6_p1148_Cosentino |
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paper:paper_00222836_v431_n6_p1148_Cosentino2023-06-08T14:48:46Z Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation 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 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 2019 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00222836_v431_n6_p1148_Cosentino http://hdl.handle.net/20.500.12110/paper_00222836_v431_n6_p1148_Cosentino |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation |
| topic_facet |
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 |
| description |
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 |
| title |
Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation |
| title_short |
Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation |
| title_full |
Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation |
| title_fullStr |
Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation |
| title_full_unstemmed |
Kat6b Modulates Oct4 and Nanog Binding to Chromatin in Embryonic Stem Cells and Is Required for Efficient Neural Differentiation |
| title_sort |
kat6b modulates oct4 and nanog binding to chromatin in embryonic stem cells and is required for efficient neural differentiation |
| publishDate |
2019 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00222836_v431_n6_p1148_Cosentino http://hdl.handle.net/20.500.12110/paper_00222836_v431_n6_p1148_Cosentino |
| _version_ |
1768541973574057984 |