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Your search keyword '"Tsaytler P"' showing total 3 results
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3 results on '"Tsaytler P"'

1. SRF promotes long-range chromatin loop formation and stem cell pluripotency

Author

Tsaytler, Pavel, Blaess, Gaby, Scholze-Wittler, Manuela, Meierhofer, David, Wittler, Lars, Koch, Frederic, and Herrmann, Bernhard G.

Abstract

Serum response factor (SRF) is a transcription factor essential for cell proliferation, differentiation, and migration and is required for primitive streak and mesoderm formation in the embryo. The canonical roles of SRF are mediated by a diverse set of context-dependent cofactors. Here, we show that SRF physically interacts with CTCF and cohesin subunits at topologically associating domain (TAD) boundaries and loop anchors. SRF promotes long-range chromatin loop formation and contributes to TAD insulation. In embryonic stem cells (ESCs), SRF associates with SOX2 and NANOG and contributes to the formation of three-dimensional (3D) pluripotency hubs. Our findings reveal additional roles of SRF in higher-order chromatin organization.

Published
2024
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2. Early neural specification of stem cells is mediated by a set of SOX2-dependent neural-associated enhancers.

Author

Tsaytler P, Blaess G, Scholze-Wittler M, Koch F, and Herrmann BG

Subjects
Animals, Mice, Neurogenesis, Gene Expression Regulation, Developmental, Octamer Transcription Factor-3 metabolism, Octamer Transcription Factor-3 genetics, Cell Differentiation genetics, Nanog Homeobox Protein metabolism, Nanog Homeobox Protein genetics, Cell Lineage genetics, Smad4 Protein metabolism, Smad4 Protein genetics, Embryonic Stem Cells metabolism, Embryonic Stem Cells cytology, Mouse Embryonic Stem Cells metabolism, Mouse Embryonic Stem Cells cytology, Chromatin metabolism, Protein Binding, SOXB1 Transcription Factors metabolism, SOXB1 Transcription Factors genetics, Enhancer Elements, Genetic, Neural Stem Cells metabolism, Neural Stem Cells cytology, Mesoderm cytology, Mesoderm metabolism
Abstract

SOX2 is a transcription factor involved in the regulatory network maintaining the pluripotency of embryonic stem cells in culture as well as in early embryos. In addition, SOX2 plays a pivotal role in neural stem cell formation and neurogenesis. How SOX2 can serve both processes has remained elusive. Here, we identified a set of SOX2-dependent neural-associated enhancers required for neural lineage priming. They form a distinct subgroup (1,898) among 8,531 OCT4/SOX2/NANOG-bound enhancers characterized by enhanced SOX2 binding and chromatin accessibility. Activation of these enhancers is triggered by neural induction of wild-type cells or by default in Smad4-ablated cells resistant to mesoderm induction and is antagonized by mesodermal transcription factors via Sox2 repression. Our data provide mechanistic insight into the transition from the pluripotency state to the early neural fate and into the regulation of early neural versus mesodermal specification in embryonic stem cells and embryos., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2024
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3. BMP4 triggers regulatory circuits specifying the cardiac mesoderm lineage.

Author

Tsaytler P, Liu J, Blaess G, Schifferl D, Veenvliet JV, Wittler L, Timmermann B, Herrmann BG, and Koch F

Subjects
Mice, Animals, Cell Differentiation genetics, Mesoderm metabolism, Transforming Growth Factor beta metabolism, Wnt Signaling Pathway genetics, Bone Morphogenetic Protein 4 metabolism, Heart, Transcription Factors metabolism
Abstract

Cardiac lineage specification in the mouse is controlled by TGFβ and WNT signaling. From fly to fish, BMP has been identified as an indispensable heart inducer. A detailed analysis of the role of Bmp4 and its effectors Smad1/5, however, was still missing. We show that Bmp4 induces cardiac mesoderm formation in murine embryonic stem cells in vitro. Bmp4 first activates Wnt3 and upregulates Nodal. pSmad1/5 and the WNT effector Tcf3 form a complex, and together with pSmad2/3 activate mesoderm enhancers and Eomes. They then cooperate with Eomes to consolidate the expression of many mesoderm factors, including T. Eomes and T form a positive- feedback loop and open additional enhancers regulating early mesoderm genes, including the transcription factor Mesp1, establishing the cardiac mesoderm lineage. In parallel, the neural fate is suppressed. Our data confirm the pivotal role of Bmp4 in cardiac mesoderm formation in the mouse. We describe in detail the consecutive and cooperative actions of three signaling pathways, BMP, WNT and Nodal, and their effector transcription factors, during cardiac mesoderm specification., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Published
2023
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