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Journal Article

Discovery and characterization of LNCSOX17 as an essential regulator in human endoderm formation

MPS-Authors
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Landshammer,  Alexandro       
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Bolondi,  Adriano       
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Kretzmer,  Helene       
Computational Genomics (Helene Kretzmer), Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Buschow,  Rene       
Microscopy and Cryo-Electron Microscopy (Head: Thorsten Mielke), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Mackowiak,  Sebastian
Precision Gene Control (Denes Hnisz), Dept. of Genome Regulation, (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Braendl,  Bjoern
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Giesselmann,  Pay       
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Tornisiello,  Rosaria       
Computational Genomics (Helene Kretzmer), Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Mielke,  Thorsten       
Microscopy and Cryo-Electron Microscopy (Head: Thorsten Mielke), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Meierhofer,  David       
Mass Spectrometry Facility (Head: David Meierhofer), Scientific Service (Head: Claudia Thurow), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Hnisz,  Denes       
Precision Gene Control (Denes Hnisz), Dept. of Genome Regulation, (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Meissner,  Alexander       
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Landshammer, A., Bolondi, A., Kretzmer, H., Much, C., Buschow, R., Rose, A., et al. (in press). Discovery and characterization of LNCSOX17 as an essential regulator in human endoderm formation. bioRxiv (Preprint Server). doi:10.1101/2022.09.12.507139.


Cite as: https://hdl.handle.net/21.11116/0000-000D-2D09-8
Abstract
Long non-coding RNAs (lncRNAs) have emerged as fundamental regulators in various biological processes, including embryonic development and cellular differentiation. Despite much progress over the past decade, the genome-wide annotation of lncRNAs remains incomplete and many known non-coding loci are still poorly characterized. Here, we report the discovery of a previously not annotated lncRNA that is transcribed upstream of the SOX17 gene and located within the same topologically associating domain. We termed it LNCSOX17 and show that it is induced following SOX17 activation but its expression is more tightly restricted to early definitive endoderm. Loss of LNCSOX17 affects crucial functions independent of SOX17 and leads to an aberrant endodermal transcriptome, signaling pathway deregulation and epithelial to mesenchymal transition defects. Consequently, cells lacking the lncRNA cannot further differentiate into more mature endodermal cell types. We identified and characterized LNCSOX17 as an essential new actor in early human endoderm, thereby further expanding the list of functionally important non-coding regulators.