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yylncT Defines a Class of Divergently Transcribed lncRNAs and Safeguards the T-mediated Mesodermal Commitment of Human PSCs.

Journal article
Authors Stefan Frank
Gaurav Ahuja
Deniz Bartsch
Nicole Russ
Wenjie Yao
Joseph Chao-Chung Kuo
Jens-Peter Derks
Vijay Suresh Akhade
Yulia Kargapolova
Theodore Georgomanolis
Jan-Erik Messling
Marie Gramm
Lilija Brant
Rizwan Rehimi
Natalia Emilse Vargas
Alina Kuroczik
Tsun-Po Yang
Raja Ghazanfar Ali Sahito
Julia Franzen
Juergen Hescheler
Agapios Sachinidis
Martin Peifer
Alvaro Rada-Iglesias
Meena Kanduri
Ivan G Costa
Chandrasekhar Kanduri
Argyris Papantonis
Leo Kurian
Published in Cell stem cell
Volume 24
Issue 2
Pages 318-327.e8
ISSN 1875-9777
Publication year 2019
Published at Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 318-327.e8
Language en
Links dx.doi.org/10.1016/j.stem.2018.11.0...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Abstract

Human protein-coding genes are often accompanied by divergently transcribed non-coding RNAs whose functions, especially in cell fate decisions, are poorly understood. Using an hESC-based cardiac differentiation model, we define a class of divergent lncRNAs, termed yin yang lncRNAs (yylncRNAs), that mirror the cell-type-specific expression pattern of their protein-coding counterparts. yylncRNAs are preferentially encoded from the genomic loci of key developmental cell fate regulators. Most yylncRNAs are spliced polyadenylated transcripts showing comparable expression patterns in vivo in mouse and in human embryos. Signifying their developmental function, the key mesoderm specifier BRACHYURY (T) is accompanied by yylncT, which localizes to the active T locus during mesoderm commitment. yylncT binds the de novo DNA methyltransferase DNMT3B, and its transcript is required for activation of the T locus, with yylncT depletion specifically abolishing mesodermal commitment. Collectively, we report a lncRNA-mediated regulatory layer safeguarding embryonic cell fate transitions.

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