Biomaterial Database

Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm. 2017

Xinan H Yang, and Rangarajan D Nadadur, and Catharina Re Hilvering, and Valerio Bianchi, and Michael Werner, and Stefan R Mazurek, and Margaret Gadek, and Kaitlyn M Shen, and Joseph Aaron Goldman, and Leonid Tyan, and Jenna Bekeny, and Johnathon M Hall, and Nutishia Lee, and Carlos Perez-Cervantes, and Ozanna Burnicka-Turek, and Kenneth D Poss, and Christopher R Weber, and Wouter de Laat, and Alexander J Ruthenburg, and Ivan P Moskowitz

Department of Pediatrics, The University of Chicago, Chicago, United States.

The noncoding genome is pervasively transcribed. Noncoding RNAs (ncRNAs) generated from enhancers have been proposed as a general facet of enhancer function and some have been shown to be required for enhancer activity. Here we examine the transcription-factor-(TF)-dependence of ncRNA expression to define enhancers and enhancer-associated ncRNAs that are involved in a TF-dependent regulatory network. TBX5, a cardiac TF, regulates a network of cardiac channel genes to maintain cardiac rhythm. We deep sequenced wildtype and Tbx5-mutant mouse atria, identifying ~2600 novel Tbx5-dependent ncRNAs. Tbx5-dependent ncRNAs were enriched for tissue-specific marks of active enhancers genome-wide. Tbx5-dependent ncRNAs emanated from regions that are enriched for TBX5-binding and that demonstrated Tbx5-dependent enhancer activity. Tbx5-dependent ncRNA transcription provided a quantitative metric of Tbx5-dependent enhancer activity, correlating with target gene expression. We identified RACER, a novel Tbx5-dependent long noncoding RNA (lncRNA) required for the expression of the calcium-handling gene Ryr2. We illustrate that TF-dependent enhancer transcription can illuminate components of TF-dependent gene regulatory networks.

UI	MeSH Term	Description	Entries
D010507	Periodicity	The tendency of a phenomenon to recur at regular intervals; in biological systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian).	Cyclicity,Rhythmicity,Biological Rhythms,Bioperiodicity,Biorhythms,Biological Rhythm,Bioperiodicities,Biorhythm,Cyclicities,Periodicities,Rhythm, Biological,Rhythmicities,Rhythms, Biological
D004742	Enhancer Elements, Genetic	Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.	Enhancer Elements,Enhancer Sequences,Element, Enhancer,Element, Genetic Enhancer,Elements, Enhancer,Elements, Genetic Enhancer,Enhancer Element,Enhancer Element, Genetic,Enhancer Sequence,Genetic Enhancer Element,Genetic Enhancer Elements,Sequence, Enhancer,Sequences, Enhancer
D006321	Heart	The hollow, muscular organ that maintains the circulation of the blood.	Hearts
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014158	Transcription, Genetic	The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.	Genetic Transcription
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D053263	Gene Regulatory Networks	Interacting DNA-encoded regulatory subsystems in the GENOME that coordinate input from activator and repressor TRANSCRIPTION FACTORS during development, cell differentiation, or in response to environmental cues. The networks function to ultimately specify expression of particular sets of GENES for specific conditions, times, or locations.	Gene Circuits,Gene Modules,Gene Networks,Transcriptional Networks,Gene Module,Circuit, Gene,Circuits, Gene,Gene Circuit,Gene Network,Gene Regulatory Network,Module, Gene,Modules, Gene,Network, Gene,Network, Gene Regulatory,Network, Transcriptional,Networks, Gene,Networks, Gene Regulatory,Networks, Transcriptional,Regulatory Network, Gene,Regulatory Networks, Gene,Transcriptional Network
D020825	T-Box Domain Proteins	Proteins containing a region of conserved sequence, about 200 amino acids long, which encodes a particular sequence specific DNA binding domain (the T-box domain). These proteins are transcription factors that control developmental pathways. The prototype of this family is the mouse Brachyury (or T) gene product.	Proteins, T-Box Domain,T Box Domain Proteins
D022661	RNA, Untranslated	RNA which does not code for protein but has some enzymatic, structural or regulatory function. Although ribosomal RNA (RNA, RIBOSOMAL) and transfer RNA (RNA, TRANSFER) are also untranslated RNAs they are not included in this scope.	Noncoding RNA,RNA, Non-Coding,RNA, Non-Peptide-Coding,RNA, Non-Protein-Coding,RNA, Noncoding,RNA, Nontranslated,npcRNA,Non-Coding RNA,Non-Peptide-Coding RNA,Non-Protein-Coding RNA,Nontranslated RNA,RNA, Non Coding,RNA, Non Peptide Coding,RNA, Non Protein Coding,Untranslated RNA