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

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

doi:10.7554/eLife.31683

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

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

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

31 Citaten (Scopus)

Samenvatting

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.

Originele taal-2	Engels
Tijdschrift	eLife
Volume	6
DOI's	https://doi.org/10.7554/eLife.31683
Status	Gepubliceerd - 27 dec. 2017

Toegang tot document

10.7554/eLife.31683

Citeer dit

Yang, X. H., Nadadur, R. D., Hilvering, C. R., Bianchi, V., Werner, M., Mazurek, S. R., Gadek, M., Shen, K. M., Goldman, J. A., Tyan, L., Bekeny, J., Hall, J. M., Lee, N., Perez-Cervantes, C., Burnicka-Turek, O., Poss, K. D., Weber, C. R., de Laat, W., Ruthenburg, A. J., & 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

@article{eed8dbe09ea24a2cac2dd265f111a9cd,

title = "Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm",

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.",

keywords = "Journal Article",

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

year = "2017",

month = dec,

day = "27",

doi = "10.7554/eLife.31683",

language = "English",

volume = "6",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

}

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 2017, 'Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm', eLife, vol. 6. https://doi.org/10.7554/eLife.31683

TY - JOUR

T1 - 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, Johnathan 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

PY - 2017/12/27

Y1 - 2017/12/27

N2 - 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.

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 - Journal Article

U2 - 10.7554/eLife.31683

DO - 10.7554/eLife.31683

M3 - Article

C2 - 29280435

SN - 2050-084X

VL - 6

JO - eLife

JF - eLife

ER -

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

Samenvatting

Toegang tot document

Vingerafdruk

Citeer dit