TY - JOUR TI - Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm AU - Yang, Xinan H AU - Nadadur, Rangarajan D AU - Hilvering, Catharina RE AU - Bianchi, Valerio AU - Werner, Michael AU - Mazurek, Stefan R AU - Gadek, Margaret AU - Shen, Kaitlyn M AU - Goldman, Joseph Aaron AU - Tyan, Leonid AU - Bekeny, Jenna AU - Hall, Johnathon M AU - Lee, Nutishia AU - Perez-Cervantes, Carlos AU - Burnicka-Turek, Ozanna AU - Poss, Kenneth D AU - Weber, Christopher R AU - de Laat, Wouter AU - Ruthenburg, Alexander J AU - Moskowitz, Ivan P A2 - Harvey, Richard P VL - 6 PY - 2017 DA - 2017/12/27 SP - e31683 C1 - eLife 2017;6:e31683 DO - 10.7554/eLife.31683 UR - https://doi.org/10.7554/eLife.31683 AB - 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. KW - Cis-regulatory element KW - enhancer KW - Transcription factor KW - non-coding RNA (ncRNA) KW - Tbx5 KW - calcium KW - long noncoding RNA (lncRNA) JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -