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

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.

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bioRxiv_Landshammer_2022.pdf (Preprint), 9MB
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Landshammer, Alexandro1, Author                 
Bolondi, Adriano1, Author                 
Kretzmer, Helene2, Author                 
Much, Christian , Author
Buschow, Rene3, Author                 
Rose, Alina, Author
Wu, Hua-Jun , Author
Mackowiak, Sebastian4, Author           
Braendl, Bjoern1, Author           
Giesselmann, Pay1, Author                 
Tornisiello, Rosaria2, Author                 
Mohan Parsi, Krishna , Author
Huey, Jack, Author
Mielke, Thorsten3, Author                 
Meierhofer, David5, Author                 
Maehr, René , Author
Hnisz, Denes4, Author                 
Michor, Franziska , Author
Rinn, John L., Author
Meissner, Alexander1, Author                 
Affiliations:
1Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              
2Computational Genomics (Helene Kretzmer), Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_3430949              
3Microscopy and Cryo-Electron Microscopy (Head: Thorsten Mielke), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479668              
4Precision Gene Control (Denes Hnisz), Dept. of Genome Regulation, (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_3014188              
5Mass Spectrometry Facility (Head: David Meierhofer), Scientific Service (Head: Claudia Thurow), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479669              

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 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.

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Language(s): eng - English
 Dates: 2022-09-13
 Publication Status: Accepted / In Press
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 Identifiers: DOI: 10.1101/2022.09.12.507139
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Title: bioRxiv (Preprint Server)
Source Genre: Web Page
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Publ. Info: New York : Cold Spring Harbor Laboratory
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