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

Publication ,  Journal Article
Yang, XH; Nadadur, RD; Hilvering, CR; Bianchi, V; Werner, M; Mazurek, SR; Gadek, M; Shen, KM; Goldman, JA; Tyan, L; Bekeny, J; Hall, JM ...
Published in: Elife
December 27, 2017

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.

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Published In

Elife

DOI

EISSN

2050-084X

Publication Date

December 27, 2017

Volume

6

Location

England

Related Subject Headings

  • Transcription, Genetic
  • T-Box Domain Proteins
  • RNA, Untranslated
  • Periodicity
  • Mice
  • Heart
  • Gene Regulatory Networks
  • Enhancer Elements, Genetic
  • Animals
  • 42 Health sciences
 

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Yang, X. H., Nadadur, R. D., Hilvering, C. R., Bianchi, V., Werner, M., Mazurek, S. R., … Moskowitz, I. P. (2017). Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm. Elife, 6. https://doi.org/10.7554/eLife.31683
Yang, Xinan H., Rangarajan D. Nadadur, Catharina Re Hilvering, Valerio Bianchi, Michael Werner, Stefan R. Mazurek, Margaret Gadek, et al. “Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm.Elife 6 (December 27, 2017). https://doi.org/10.7554/eLife.31683.
Yang XH, Nadadur RD, Hilvering CR, Bianchi V, Werner M, Mazurek SR, et al. Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm. Elife. 2017 Dec 27;6.
Yang, Xinan H., et al. “Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm.Elife, vol. 6, Dec. 2017. Pubmed, doi:10.7554/eLife.31683.
Yang XH, Nadadur RD, Hilvering CR, Bianchi V, Werner M, Mazurek SR, Gadek M, Shen KM, Goldman JA, Tyan L, Bekeny J, Hall JM, Lee N, Perez-Cervantes C, Burnicka-Turek O, Poss KD, Weber CR, de Laat W, Ruthenburg AJ, Moskowitz IP. Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm. Elife. 2017 Dec 27;6.

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

December 27, 2017

Volume

6

Location

England

Related Subject Headings

  • Transcription, Genetic
  • T-Box Domain Proteins
  • RNA, Untranslated
  • Periodicity
  • Mice
  • Heart
  • Gene Regulatory Networks
  • Enhancer Elements, Genetic
  • Animals
  • 42 Health sciences