Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm
| Autor: | Jenna Bekeny, Christopher R. Weber, Margaret Gadek, Wouter de Laat, Xinan Yang, Valerio Bianchi, Joseph A. Goldman, Catharina R.E. Hilvering, Kenneth D. Poss, Stefan R Mazurek, Nutishia Lee, Rangarajan D. Nadadur, Alexander J. Ruthenburg, Ivan P. Moskowitz, Kaitlyn M Shen, Michael S. Werner, Leonid Tyan, Ozanna Burnicka-Turek, Carlos Perez-Cervantes, Johnathon M Hall |
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| Přispěvatelé: | Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Periodicity RNA Untranslated HL-1 Transcription Genetic Mouse Untranslated/biosynthesis Gene regulatory network Mice Transcription (biology) Gene Regulatory Networks Biology (General) CELL-LINE General Neuroscience Heart General Medicine Non-coding RNA Tbx5 Long non-coding RNA Heart/physiology 3. Good health Enhancer Elements Genetic Genomics and Evolutionary Biology Genes and Chromosomes T-Box Domain Proteins/metabolism Medicine Cis-regulatory element Transcription Research Article PACKAGE EXPRESSION Enhancer Elements BROWSER QH301-705.5 DATABASE Science NcRNA transcription Computational biology Biology General Biochemistry Genetics and Molecular Biology RNAS 03 medical and health sciences Genetic non-coding RNA (ncRNA) Journal Article Animals Enhancer Gene Transcription factor calcium General Immunology and Microbiology RNA Untranslated/biosynthesis long noncoding RNA (lncRNA) 030104 developmental biology RNA enhancer T-Box Domain Proteins |
| Zdroj: | eLife, 6. eLife Sciences Publications eLife eLife, Vol 6 (2017) Elife, 6:31683. eLife Sciences Publications, Ltd |
| ISSN: | 2050-084X |
| DOI: | 10.7554/elife.31683 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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