Abstract
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.
Original language | English |
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Article number | 31683 |
Pages (from-to) | e31683 |
Number of pages | 21 |
Journal | Elife |
Volume | 6 |
DOIs | |
Publication status | Published - 27 Dec 2017 |
Externally published | Yes |
Keywords
- Animals
- Enhancer Elements, Genetic
- Gene Regulatory Networks
- Heart/physiology
- Mice
- Periodicity
- RNA, Untranslated/biosynthesis
- T-Box Domain Proteins/metabolism
- Transcription, Genetic
- BROWSER
- RNAS
- HL-1
- DATABASE
- PACKAGE
- EXPRESSION
- CELL-LINE