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Article ; Online: Author Correction: Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network.

Grapotte, Mathys / Saraswat, Manu / Bessière, Chloé / Menichelli, Christophe / Ramilowski, Jordan A / Severin, Jessica / Hayashizaki, Yoshihide / Itoh, Masayoshi / Tagami, Michihira / Murata, Mitsuyoshi / Kojima-Ishiyama, Miki / Noma, Shohei / Noguchi, Shuhei / Kasukawa, Takeya / Hasegawa, Akira / Suzuki, Harukazu / Nishiyori-Sueki, Hiromi / Frith, Martin C / Chatelain, Clément /

Carninci, Piero / de Hoon, Michiel J L / Wasserman, Wyeth W / Bréhélin, Laurent / Lecellier, Charles-Henri

Nature communications

2022 Volume 13, Issue 1, Page(s) 1200

Language	English
Publishing date	2022-03-01
Publishing country	England
Document type	Published Erratum
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-28758-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: LETR1 is a lymphatic endothelial-specific lncRNA governing cell proliferation and migration through KLF4 and SEMA3C.

Ducoli, Luca / Agrawal, Saumya / Sibler, Eliane / Kouno, Tsukasa / Tacconi, Carlotta / Hon, Chung-Chao / Berger, Simone D / Müllhaupt, Daniela / He, Yuliang / Kim, Jihye / D'Addio, Marco / Dieterich, Lothar C / Carninci, Piero / de Hoon, Michiel J L / Shin, Jay W / Detmar, Michael

Nature communications

2021 Volume 12, Issue 1, Page(s) 925

Abstract: Recent studies have revealed the importance of long noncoding RNAs (lncRNAs) as tissue-specific regulators of gene expression. There is ample evidence that distinct types of vasculature undergo tight transcriptional control to preserve their structure, ... ...

Abstract	Recent studies have revealed the importance of long noncoding RNAs (lncRNAs) as tissue-specific regulators of gene expression. There is ample evidence that distinct types of vasculature undergo tight transcriptional control to preserve their structure, identity, and functions. We determine a comprehensive map of lineage-specific lncRNAs in human dermal lymphatic and blood vascular endothelial cells (LECs and BECs), combining RNA-Seq and CAGE-Seq. Subsequent antisense oligonucleotide-knockdown transcriptomic profiling of two LEC- and two BEC-specific lncRNAs identifies LETR1 as a critical gatekeeper of the global LEC transcriptome. Deep RNA-DNA, RNA-protein interaction studies, and phenotype rescue analyses reveal that LETR1 is a nuclear trans-acting lncRNA modulating, via key epigenetic factors, the expression of essential target genes, including KLF4 and SEMA3C, governing the growth and migratory ability of LECs. Together, our study provides several lines of evidence supporting the intriguing concept that every cell type expresses precise lncRNA signatures to control lineage-specific regulatory programs.
MeSH term(s)	Cell Movement ; Cell Proliferation ; Endothelial Cells/cytology ; Endothelial Cells/metabolism ; Gene Expression Regulation ; Humans ; Kruppel-Like Factor 4 ; Kruppel-Like Transcription Factors/genetics ; Kruppel-Like Transcription Factors/metabolism ; RNA, Long Noncoding ; Semaphorins/genetics ; Semaphorins/metabolism
Chemical Substances	KLF4 protein, human ; Kruppel-Like Factor 4 ; Kruppel-Like Transcription Factors ; RNA, Long Noncoding ; Sema3C protein, human ; Semaphorins
Language	English
Publishing date	2021-02-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-21217-0
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Article ; Online: LETR1 is a lymphatic endothelial-specific lncRNA governing cell proliferation and migration through KLF4 and SEMA3C

Luca Ducoli / Saumya Agrawal / Eliane Sibler / Tsukasa Kouno / Carlotta Tacconi / Chung-Chao Hon / Simone D. Berger / Daniela Müllhaupt / Yuliang He / Jihye Kim / Marco D’Addio / Lothar C. Dieterich / Piero Carninci / Michiel J. L. de Hoon / Jay W. Shin / Michael Detmar

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 22

Abstract: Long noncoding RNAs regulate tissue-specific gene expression. Here the authors profile lineage-specific lncRNAs in human dermal lymphatic and blood vascular endothelial cells (LECs and BECs) and show a role of LEC-specific lncRNA, LETR1, in cell ... ...

Abstract	Long noncoding RNAs regulate tissue-specific gene expression. Here the authors profile lineage-specific lncRNAs in human dermal lymphatic and blood vascular endothelial cells (LECs and BECs) and show a role of LEC-specific lncRNA, LETR1, in cell proliferation and migration.
Keywords	Science ; Q
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The choice of negative control antisense oligonucleotides dramatically impacts downstream analysis depending on the cellular background.

Ducoli, Luca / Agrawal, Saumya / Hon, Chung-Chau / Ramilowski, Jordan A / Sibler, Eliane / Tagami, Michihira / Itoh, Masayoshi / Kondo, Naoto / Abugessaisa, Imad / Hasegawa, Akira / Kasukawa, Takeya / Suzuki, Harukazu / Carninci, Piero / Shin, Jay W / de Hoon, Michiel J L / Detmar, Michael

BMC genomic data

2021 Volume 22, Issue 1, Page(s) 33

Abstract: Background: The lymphatic and the blood vasculature are closely related systems that collaborate to ensure the organism's physiological function. Despite their common developmental origin, they present distinct functional fates in adulthood that rely on ...

Abstract	Background: The lymphatic and the blood vasculature are closely related systems that collaborate to ensure the organism's physiological function. Despite their common developmental origin, they present distinct functional fates in adulthood that rely on robust lineage-specific regulatory programs. The recent technological boost in sequencing approaches unveiled long noncoding RNAs (lncRNAs) as prominent regulatory players of various gene expression levels in a cell-type-specific manner. Results: To investigate the potential roles of lncRNAs in vascular biology, we performed antisense oligonucleotide (ASO) knockdowns of lncRNA candidates specifically expressed either in human lymphatic or blood vascular endothelial cells (LECs or BECs) followed by Cap Analysis of Gene Expression (CAGE-Seq). Here, we describe the quality control steps adopted in our analysis pipeline before determining the knockdown effects of three ASOs per lncRNA target on the LEC or BEC transcriptomes. In this regard, we especially observed that the choice of negative control ASOs can dramatically impact the conclusions drawn from the analysis depending on the cellular background. Conclusion: In conclusion, the comparison of negative control ASO effects on the targeted cell type transcriptomes highlights the essential need to select a proper control set of multiple negative control ASO based on the investigated cell types.
MeSH term(s)	Adult ; Endothelial Cells/metabolism ; Gene Knockdown Techniques/methods ; Gene Knockdown Techniques/standards ; Humans ; Lymphatic System/cytology ; Lymphatic System/metabolism ; Oligonucleotides, Antisense/genetics ; Oligonucleotides, Antisense/standards ; Organ Specificity/genetics ; RNA, Long Noncoding/genetics ; Transcriptome
Chemical Substances	Oligonucleotides, Antisense ; RNA, Long Noncoding
Language	English
Publishing date	2021-09-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2730-6844
ISSN (online)	2730-6844
DOI	10.1186/s12863-021-00992-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Author Correction

Mathys Grapotte / Manu Saraswat / Chloé Bessière / Christophe Menichelli / Jordan A. Ramilowski / Jessica Severin / Yoshihide Hayashizaki / Masayoshi Itoh / Michihira Tagami / Mitsuyoshi Murata / Miki Kojima-Ishiyama / Shohei Noma / Shuhei Noguchi / Takeya Kasukawa / Akira Hasegawa / Harukazu Suzuki / Hiromi Nishiyori-Sueki / Martin C. Frith / FANTOM consortium /

Clément Chatelain / Piero Carninci / Michiel J. L. de Hoon / Wyeth W. Wasserman / Laurent Bréhélin / Charles-Henri Lecellier

Nature Communications, Vol 13, Iss 1, Pp 1-

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

2022 Volume 1

Keywords	Science ; Q
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The choice of negative control antisense oligonucleotides dramatically impacts downstream analysis depending on the cellular background

Ducoli, Luca / Agrawal, Saumya / Hon, Chung-Chau / Ramilowski, Jordan A. / Sibler, Eliane / Tagami, Michihira / Itoh, Masayoshi / Kondo, Naoto / Abugessaisa, Imad / Hasegawa, Akira / Kasukawa, Takeya / Suzuki, Harukazu / Carninci, Piero / Shin, Jay W. / de Hoon, Michiel J. L. / Detmar, Michael

BMC genomic data. 2021 Dec., v. 22, no. 1

2021

Abstract: BACKGROUND: The lymphatic and the blood vasculature are closely related systems that collaborate to ensure the organism’s physiological function. Despite their common developmental origin, they present distinct functional fates in adulthood that rely on ... ...

Abstract	BACKGROUND: The lymphatic and the blood vasculature are closely related systems that collaborate to ensure the organism’s physiological function. Despite their common developmental origin, they present distinct functional fates in adulthood that rely on robust lineage-specific regulatory programs. The recent technological boost in sequencing approaches unveiled long noncoding RNAs (lncRNAs) as prominent regulatory players of various gene expression levels in a cell-type-specific manner. RESULTS: To investigate the potential roles of lncRNAs in vascular biology, we performed antisense oligonucleotide (ASO) knockdowns of lncRNA candidates specifically expressed either in human lymphatic or blood vascular endothelial cells (LECs or BECs) followed by Cap Analysis of Gene Expression (CAGE-Seq). Here, we describe the quality control steps adopted in our analysis pipeline before determining the knockdown effects of three ASOs per lncRNA target on the LEC or BEC transcriptomes. In this regard, we especially observed that the choice of negative control ASOs can dramatically impact the conclusions drawn from the analysis depending on the cellular background. CONCLUSION: In conclusion, the comparison of negative control ASO effects on the targeted cell type transcriptomes highlights the essential need to select a proper control set of multiple negative control ASO based on the investigated cell types.
Keywords	adulthood ; blood ; gene expression ; genomics ; humans ; oligonucleotides ; quality control ; transcriptome
Language	English
Dates of publication	2021-12
Size	p. 33.
Publishing place	BioMed Central
Document type	Article
ISSN	2730-6844
DOI	10.1186/s12863-021-00992-1
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network.

Carninci, Piero / de Hoon, Michiel J L / Wasserman, Wyeth W / Bréhélin, Laurent / Lecellier, Charles-Henri

Nature communications

2021 Volume 12, Issue 1, Page(s) 3297

Abstract: Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and ... ...

Abstract	Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.
MeSH term(s)	A549 Cells ; Animals ; Base Sequence ; Computational Biology/methods ; Deep Learning ; Enhancer Elements, Genetic ; Genome, Human ; High-Throughput Nucleotide Sequencing ; Humans ; Mice ; Microsatellite Repeats ; Neural Networks, Computer ; Neurodegenerative Diseases/diagnosis ; Neurodegenerative Diseases/genetics ; Neurodegenerative Diseases/metabolism ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Transcription Initiation Site ; Transcription Initiation, Genetic
Language	English
Publishing date	2021-06-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-23143-7
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Article ; Online: Hierarchical evolution of the bacterial sporulation network.

de Hoon, Michiel J L / Eichenberger, Patrick / Vitkup, Dennis

Current biology : CB

2010 Volume 20, Issue 17, Page(s) R735–45

Abstract: Genome sequencing of multiple species makes it possible to understand the main principles behind the evolution of developmental regulatory networks. It is especially interesting to analyze the evolution of well-defined model systems in which conservation ...

Abstract	Genome sequencing of multiple species makes it possible to understand the main principles behind the evolution of developmental regulatory networks. It is especially interesting to analyze the evolution of well-defined model systems in which conservation patterns can be directly correlated with the functional roles of various network components. Endospore formation (sporulation), extensively studied in Bacillus subtilis, is driven by such a model bacterial network of cellular development and differentiation. In this review, we analyze the evolution of the sporulation network in multiple endospore-forming bacteria. Importantly, the network evolution is not random but primarily follows the hierarchical organization and functional logic of the sporulation process. Specifically, the sporulation sigma factors and the master regulator of sporulation, Spo0A, are conserved in all considered spore-formers. The sequential activation of these global regulators is also strongly conserved. The feed-forward loops, which are likely used to fine-tune waves of gene expression within regulatory modules, show an intermediate level of conservation. These loops are less conserved than the sigma factors but significantly more than the structural sporulation genes, which form the lowest level in the functional and evolutionary hierarchy of the sporulation network. Interestingly, in spore-forming bacteria, gene regulation is more conserved than gene presence for sporulation genes, while the opposite is true for non-sporulation genes. The observed patterns suggest that, by understanding the functional organization of a developmental network in a model organism, it is possible to understand the logic behind the evolution of this network in multiple related species.
MeSH term(s)	Bacillus subtilis/classification ; Bacillus subtilis/genetics ; Bacillus subtilis/physiology ; DNA Replication ; Evolution, Molecular ; Gene Regulatory Networks ; Phylogeny ; Spores, Bacterial ; Transcription, Genetic
Language	English
Publishing date	2010-09-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2010.06.031
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Article ; Online: Recounting the FANTOM CAGE-Associated Transcriptome.

Imada, Eddie Luidy / Sanchez, Diego Fernando / Collado-Torres, Leonardo / Wilks, Christopher / Matam, Tejasvi / Dinalankara, Wikum / Stupnikov, Aleksey / Lobo-Pereira, Francisco / Yip, Chi-Wai / Yasuzawa, Kayoko / Kondo, Naoto / Itoh, Masayoshi / Suzuki, Harukazu / Kasukawa, Takeya / Hon, Chung-Chau / de Hoon, Michiel J L / Shin, Jay W / Carninci, Piero / Jaffe, Andrew E /

Leek, Jeffrey T / Favorov, Alexander / Franco, Gloria R / Langmead, Ben / Marchionni, Luigi

Genome research

2020 Volume 30, Issue 7, Page(s) 1073–1081

Abstract: Long noncoding RNAs (lncRNAs) have emerged as key coordinators of biological and cellular processes. Characterizing lncRNA expression across cells and tissues is key to understanding their role in determining phenotypes, including human diseases. We ... ...

Abstract	Long noncoding RNAs (lncRNAs) have emerged as key coordinators of biological and cellular processes. Characterizing lncRNA expression across cells and tissues is key to understanding their role in determining phenotypes, including human diseases. We present here FC-R2, a comprehensive expression atlas across a broadly defined human transcriptome, inclusive of over 109,000 coding and noncoding genes, as described in the FANTOM CAGE-Associated Transcriptome (FANTOM-CAT) study. This atlas greatly extends the gene annotation used in the original
MeSH term(s)	Databases, Genetic ; Enhancer Elements, Genetic ; Gene Expression Profiling ; Genome, Human ; Humans ; Neoplasms/genetics ; Organ Specificity ; Prognosis ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; RNA, Messenger/metabolism ; Transcriptome
Chemical Substances	RNA, Long Noncoding ; RNA, Messenger
Language	English
Publishing date	2020-02-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.254656.119
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Article ; Online: Comparative transcriptomics of primary cells in vertebrates.

Alam, Tanvir / Agrawal, Saumya / Severin, Jessica / Young, Robert S / Andersson, Robin / Arner, Erik / Hasegawa, Akira / Lizio, Marina / Ramilowski, Jordan A / Abugessaisa, Imad / Ishizu, Yuri / Noma, Shohei / Tarui, Hiroshi / Taylor, Martin S / Lassmann, Timo / Itoh, Masayoshi / Kasukawa, Takeya / Kawaji, Hideya / Marchionni, Luigi /

Sheng, Guojun / R R Forrest, Alistair / Khachigian, Levon M / Hayashizaki, Yoshihide / Carninci, Piero / de Hoon, Michiel J L

Genome research

2020 Volume 30, Issue 7, Page(s) 951–961

Abstract: Gene expression profiles in homologous tissues have been observed to be different between species, which may be due to differences between species in the gene expression program in each cell type, but may also reflect differences in cell type composition ...

Abstract	Gene expression profiles in homologous tissues have been observed to be different between species, which may be due to differences between species in the gene expression program in each cell type, but may also reflect differences in cell type composition of each tissue in different species. Here, we compare expression profiles in matching primary cells in human, mouse, rat, dog, and chicken using Cap Analysis Gene Expression (CAGE) and short RNA (sRNA) sequencing data from FANTOM5. While we find that expression profiles of orthologous genes in different species are highly correlated across cell types, in each cell type many genes were differentially expressed between species. Expression of genes with products involved in transcription, RNA processing, and transcriptional regulation was more likely to be conserved, while expression of genes encoding proteins involved in intercellular communication was more likely to have diverged during evolution. Conservation of expression correlated positively with the evolutionary age of genes, suggesting that divergence in expression levels of genes critical for cell function was restricted during evolution. Motif activity analysis showed that both promoters and enhancers are activated by the same transcription factors in different species. An analysis of expression levels of mature miRNAs and of primary miRNAs identified by CAGE revealed that evolutionary old miRNAs are more likely to have conserved expression patterns than young miRNAs. We conclude that key aspects of the regulatory network are conserved, while differential expression of genes involved in cell-to-cell communication may contribute greatly to phenotypic differences between species.
MeSH term(s)	Animals ; Chickens/genetics ; Dogs ; Evolution, Molecular ; Gene Expression Profiling ; Gene Regulatory Networks ; Humans ; Mice ; MicroRNAs/metabolism ; Nucleotide Motifs ; Principal Component Analysis ; Promoter Regions, Genetic ; Rats ; Species Specificity ; Transcription Factors/metabolism ; Transcriptome
Chemical Substances	MicroRNAs ; Transcription Factors
Language	English
Publishing date	2020-07-27
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.255679.119
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