yylncT Defines a Class of Divergently Transcribed lncRNAs and Safeguards the T-mediated Mesodermal Commitment of Human PSCs
| Autor: | Agapios Sachinidis, Natalia Emilse Vargas, Juergen Hescheler, Julia Franzen, Ivan G. Costa, Deniz Bartsch, Marie Gramm, Lilija Brant, Argyris Papantonis, Alvaro Rada-Iglesias, Joseph Chao-Chung Kuo, Nicole Russ, Meena Kanduri, Tsun-Po Yang, Chandrasekhar Kanduri, Jens-Peter Derks, Leo Kurian, Gaurav Ahuja, Jan-Erik Messling, Theodore Georgomanolis, Wenjie Yao, Rizwan Rehimi, Stefan Frank, Yulia Kargapolova, Martin Peifer, Vijay Suresh Akhade, Raja Ghazanfar Ali Sahito, Alina Kuroczik |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Fetal Proteins
Pluripotent Stem Cells Brachyury Mesoderm Polyadenylation Transcription Genetic DNMT3B Human Embryonic Stem Cells Locus (genetics) Biology DNA methyltransferase Cell Line 03 medical and health sciences Mice 0302 clinical medicine Genetics medicine Animals Humans Cell Lineage DNA (Cytosine-5-)-Methyltransferases RNA Messenger Gene 030304 developmental biology 0303 health sciences Cell Differentiation Cell Biology Embryonic stem cell Cell biology medicine.anatomical_structure Genetic Loci embryonic structures Molecular Medicine RNA Long Noncoding T-Box Domain Proteins 030217 neurology & neurosurgery |
| Zdroj: | Cell stem cell. 24(2) |
| ISSN: | 1875-9777 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|