Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease
Abstract
We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Through a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancersmore »
- Authors:
-
- Univ. of Lausanne Medical School, Lausanne (Switzerland)
- Univ. of Lausanne Medical School, Lausanne (Switzerland). VitalIT, Swiss Institute of Bioinformatics
- Univ. of Lausanne Medical School, Lausanne (Switzerland). Cardiovascular Assessment Facility
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); DOE Joint Genome Inst., Walnut Creek, CA (United States)
- Centre for Genomic Regulation, Barcelona (Spain)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1257346
- Grant/Contract Number:
- AC02-05CH11231; R01HG003988
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Molecular and Cellular Cardiology
- Additional Journal Information:
- Journal Volume: 76; Journal Issue: C; Journal ID: ISSN 0022-2828
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Ounzain, Samir, Pezzuto, Iole, Micheletti, Rudi, Burdet, Frédéric, Sheta, Razan, Nemir, Mohamed, Gonzales, Christine, Sarre, Alexandre, Alexanian, Michael, Blow, Matthew J., May, Dalit, Johnson, Rory, Dauvillier, Jérôme, Pennacchio, Len A., and Pedrazzini, Thierry. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease. United States: N. p., 2014.
Web. doi:10.1016/j.yjmcc.2014.08.009.
Ounzain, Samir, Pezzuto, Iole, Micheletti, Rudi, Burdet, Frédéric, Sheta, Razan, Nemir, Mohamed, Gonzales, Christine, Sarre, Alexandre, Alexanian, Michael, Blow, Matthew J., May, Dalit, Johnson, Rory, Dauvillier, Jérôme, Pennacchio, Len A., & Pedrazzini, Thierry. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease. United States. https://doi.org/10.1016/j.yjmcc.2014.08.009
Ounzain, Samir, Pezzuto, Iole, Micheletti, Rudi, Burdet, Frédéric, Sheta, Razan, Nemir, Mohamed, Gonzales, Christine, Sarre, Alexandre, Alexanian, Michael, Blow, Matthew J., May, Dalit, Johnson, Rory, Dauvillier, Jérôme, Pennacchio, Len A., and Pedrazzini, Thierry. Tue .
"Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease". United States. https://doi.org/10.1016/j.yjmcc.2014.08.009. https://www.osti.gov/servlets/purl/1257346.
@article{osti_1257346,
title = {Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease},
author = {Ounzain, Samir and Pezzuto, Iole and Micheletti, Rudi and Burdet, Frédéric and Sheta, Razan and Nemir, Mohamed and Gonzales, Christine and Sarre, Alexandre and Alexanian, Michael and Blow, Matthew J. and May, Dalit and Johnson, Rory and Dauvillier, Jérôme and Pennacchio, Len A. and Pedrazzini, Thierry},
abstractNote = {We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Through a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.},
doi = {10.1016/j.yjmcc.2014.08.009},
journal = {Journal of Molecular and Cellular Cardiology},
number = C,
volume = 76,
place = {United States},
year = {Tue Aug 19 00:00:00 EDT 2014},
month = {Tue Aug 19 00:00:00 EDT 2014}
}
Web of Science
Works referenced in this record:
Gene Regulatory Networks in the Evolution and Development of the Heart
journal, September 2006
- Olson, E. N.
- Science, Vol. 313, Issue 5795
Transcriptional Regulation of Vertebrate Cardiac Morphogenesis
journal, March 2002
- Bruneau, Benoit G.
- Circulation Research, Vol. 90, Issue 5
The developmental genetics of congenital heart disease
journal, February 2008
- Bruneau, Benoit G.
- Nature, Vol. 451, Issue 7181
Enhancer function: new insights into the regulation of tissue-specific gene expression
journal, March 2011
- Ong, Chin-Tong; Corces, Victor G.
- Nature Reviews Genetics, Vol. 12, Issue 4
Dynamic and Coordinated Epigenetic Regulation of Developmental Transitions in the Cardiac Lineage
journal, September 2012
- Wamstad, Joseph A.; Alexander, Jeffrey M.; Truty, Rebecca M.
- Cell, Vol. 151, Issue 1
A Transcription Factor Collective Defines Cardiac Cell Fate and Reflects Lineage History
journal, February 2012
- Junion, Guillaume; Spivakov, Mikhail; Girardot, Charles
- Cell, Vol. 148, Issue 3
Intergenic transcription and transinduction of the human beta -globin locus
journal, October 1997
- Ashe, H. L.; Monks, J.; Wijgerde, M.
- Genes & Development, Vol. 11, Issue 19
A Large Fraction of Extragenic RNA Pol II Transcription Sites Overlap Enhancers
journal, May 2010
- De Santa, Francesca; Barozzi, Iros; Mietton, Flore
- PLoS Biology, Vol. 8, Issue 5
Widespread transcription at neuronal activity-regulated enhancers
journal, April 2010
- Kim, Tae-Kyung; Hemberg, Martin; Gray, Jesse M.
- Nature, Vol. 465, Issue 7295
Long Noncoding RNAs with Enhancer-like Function in Human Cells
journal, October 2010
- Ørom, Ulf Andersson; Derrien, Thomas; Beringer, Malte
- Cell, Vol. 143, Issue 1
Intragenic Enhancers Act as Alternative Promoters
journal, February 2012
- Kowalczyk, Monika S.; Hughes, Jim R.; Garrick, David
- Molecular Cell, Vol. 45, Issue 4
Activating RNAs associate with Mediator to enhance chromatin architecture and transcription
journal, February 2013
- Lai, Fan; Orom, Ulf A.; Cesaroni, Matteo
- Nature, Vol. 494, Issue 7438
A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression
journal, March 2011
- Wang, Kevin C.; Yang, Yul W.; Liu, Bo
- Nature, Vol. 472, Issue 7341
Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression
journal, July 2009
- Khalil, Ahmad M.; Guttman, Mitchell; Huarte, Maite
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 28
RNA traffic control of chromatin complexes
journal, April 2010
- Koziol, Magdalena J.; Rinn, John L.
- Current Opinion in Genetics & Development, Vol. 20, Issue 2
RNA regulation of epigenetic processes
journal, January 2009
- Mattick, John S.; Amaral, Paulo P.; Dinger, Marcel E.
- BioEssays, Vol. 31, Issue 1
The medicinal leech genome encodes 21 innexin genes: different combinations are expressed by identified central neurons
journal, February 2012
- Kandarian, Brandon; Sethi, Jasmine; Wu, Allan
- Development Genes and Evolution, Vol. 222, Issue 1
eRNAs Are Required for p53-Dependent Enhancer Activity and Gene Transcription
journal, February 2013
- Melo, Carlos A.; Drost, Jarno; Wijchers, Patrick J.
- Molecular Cell, Vol. 49, Issue 3
Large-scale discovery of enhancers from human heart tissue
journal, December 2011
- May, Dalit; Blow, Matthew J.; Kaplan, Tommy
- Nature Genetics, Vol. 44, Issue 1
ChIP-Seq identification of weakly conserved heart enhancers
journal, August 2010
- Blow, Matthew J.; McCulley, David J.; Li, Zirong
- Nature Genetics, Vol. 42, Issue 9
Co-occupancy by multiple cardiac transcription factors identifies transcriptional enhancers active in heart
journal, March 2011
- He, A.; Kong, S. W.; Ma, Q.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 14
Marking Embryonic Stem Cells with a 2A Self-Cleaving Peptide: A NKX2-5 Emerald GFP BAC Reporter
journal, July 2008
- Hsiao, Edward C.; Yoshinaga, Yuko; Nguyen, Trieu D.
- PLoS ONE, Vol. 3, Issue 7
Retinoic Acid Accelerates Embryonic Stem Cell-Derived Cardiac Differentiation and Enhances Development of Ventricular Cardiomyocytes
journal, June 1997
- Wobus, Anna M.; Kaomei, Guan; Shan, Jin
- Journal of Molecular and Cellular Cardiology, Vol. 29, Issue 6
Isolation of Cardiovascular Precursor Cells from the Human Fetal Heart
journal, January 2012
- Gonzales, Christine; Ullrich, Nina D.; Gerber, Stefan
- Tissue Engineering Part A, Vol. 18, Issue 1-2
Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks
journal, March 2012
- Trapnell, Cole; Roberts, Adam; Goff, Loyal
- Nature Protocols, Vol. 7, Issue 3
Modulation of adverse cardiac remodeling by STARS, a mediator of MEF2 signaling and SRF activity
journal, May 2007
- Kuwahara, Koichiro; Pipes, Gordon C. Teg; McAnally, John
- Journal of Clinical Investigation, Vol. 117, Issue 5
Differentiation of Mouse Embryonic Stem Cells into Cardiomyocytes via the Hanging‐Drop and Mass Culture Methods
journal, October 2010
- Fuegemann, Christopher J.; Samraj, Ajoy K.; Walsh, Stuart
- Current Protocols in Stem Cell Biology, Vol. 15, Issue 1
Differentiation of Beating Cardiac Muscle Cells from a Derivative of P19 Embryonal Carcinoma Cells.
journal, January 1996
- Habara-Ohkubo, Akemi
- Cell Structure and Function, Vol. 21, Issue 2
The T-box transcription factor Eomesodermin acts upstream of Mesp1 to specify cardiac mesoderm during mouse gastrulation
journal, August 2011
- Costello, Ita; Pimeisl, Inga-Marie; Dräger, Sarah
- Nature Cell Biology, Vol. 13, Issue 9
Chromatin signatures at transcriptional start sites separate two equally populated yet distinct classes of intergenic long noncoding RNAs
journal, January 2013
- Marques, Ana C.; Hughes, Jim; Graham, Bryony
- Genome Biology, Vol. 14, Issue 11
A User's Guide to the Encyclopedia of DNA Elements (ENCODE)
journal, April 2011
- ,
- PLoS Biology, Vol. 9, Issue 4
A map of the cis-regulatory sequences in the mouse genome
journal, July 2012
- Shen, Yin; Yue, Feng; McCleary, David F.
- Nature, Vol. 488, Issue 7409
An overview of endothelin signaling in the cardiac myocyte
journal, August 2003
- Sugden, P.
- Journal of Molecular and Cellular Cardiology, Vol. 35, Issue 8
Tbx20 regulates a genetic program essential to adult mouse cardiomyocyte function
journal, December 2011
- Shen, Tao; Aneas, Ivy; Sakabe, Noboru
- Journal of Clinical Investigation, Vol. 121, Issue 12
Genome-wide analysis of histone marks identifying an epigenetic signature of promoters and enhancers underlying cardiac hypertrophy
journal, November 2013
- Papait, R.; Cattaneo, P.; Kunderfranco, P.
- Proceedings of the National Academy of Sciences, Vol. 110, Issue 50
ChIP-seq accurately predicts tissue-specific activity of enhancers
journal, February 2009
- Visel, Axel; Blow, Matthew J.; Li, Zirong
- Nature, Vol. 457, Issue 7231
lincRNAs act in the circuitry controlling pluripotency and differentiation
journal, August 2011
- Guttman, Mitchell; Donaghey, Julie; Carey, Bryce W.
- Nature, Vol. 477, Issue 7364
Targeted RNA sequencing reveals the deep complexity of the human transcriptome
journal, November 2011
- Mercer, Tim R.; Gerhardt, Daniel J.; Dinger, Marcel E.
- Nature Biotechnology, Vol. 30, Issue 1
Non-coding RNAs as regulators of embryogenesis
journal, January 2011
- Pauli, Andrea; Rinn, John L.; Schier, Alexander F.
- Nature Reviews Genetics, Vol. 12, Issue 2
Modular regulatory principles of large non-coding RNAs
journal, February 2012
- Guttman, Mitchell; Rinn, John L.
- Nature, Vol. 482, Issue 7385
A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?
journal, August 2011
- Salmena, Leonardo; Poliseno, Laura; Tay, Yvonne
- Cell, Vol. 146, Issue 3
Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses
journal, September 2011
- Cabili, M. N.; Trapnell, C.; Goff, L.
- Genes & Development, Vol. 25, Issue 18
Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15INK4B tumor suppressor gene
journal, December 2010
- Kotake, Y.; Nakagawa, T.; Kitagawa, K.
- Oncogene, Vol. 30, Issue 16
Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs
journal, June 2007
- Rinn, John L.; Kertesz, Michael; Wang, Jordon K.
- Cell, Vol. 129, Issue 7
Polycomb Repressive Complex 2 Regulates Normal Development of the Mouse Heart
journal, February 2012
- He, Aibin; Ma, Qing; Cao, Jingjing
- Circulation Research, Vol. 110, Issue 3
Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasis
journal, January 2012
- Delgado-Olguín, Paul; Huang, Yu; Li, Xue
- Nature Genetics, Vol. 44, Issue 3
Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment
journal, January 2013
- Klattenhoff, Carla A.; Scheuermann, Johanna C.; Surface, Lauren E.
- Cell, Vol. 152, Issue 3
The Tissue-Specific lncRNA Fendrr Is an Essential Regulator of Heart and Body Wall Development in the Mouse
journal, January 2013
- Grote, Phillip; Wittler, Lars; Hendrix, David
- Developmental Cell, Vol. 24, Issue 2
Association Between the Coronary Artery Disease Risk Locus on Chromosome 9p21.3 and Abdominal Aortic Aneurysm
journal, October 2008
- Bown, Matthew J.; Braund, Peter S.; Thompson, John
- Circulation: Cardiovascular Genetics, Vol. 1, Issue 1
Four Genetic Loci Influencing Electrocardiographic Indices of Left Ventricular Hypertrophy
journal, December 2011
- Shah, Sonia; Nelson, Christopher P.; Gaunt, Tom R.
- Circulation: Cardiovascular Genetics, Vol. 4, Issue 6
Evidence of Abundant Purifying Selection in Humans for Recently Acquired Regulatory Functions
journal, September 2012
- Ward, L. D.; Kellis, M.
- Science, Vol. 337, Issue 6102
Long-Range Control of Gene Expression: Emerging Mechanisms and Disruption in Disease
journal, January 2005
- Kleinjan, Dirk A.; van Heyningen, Veronica
- The American Journal of Human Genetics, Vol. 76, Issue 1
Differentiation of Mouse Embryonic Stem Cells into Cardiomyocytes via the Hanging‐Drop and Mass Culture Methods
journal, October 2010
- Fuegemann, Christopher J.; Samraj, Ajoy K.; Walsh, Stuart
- Current Protocols in Stem Cell Biology, Vol. 15, Issue 1
Retinoic Acid Accelerates Embryonic Stem Cell-Derived Cardiac Differentiation and Enhances Development of Ventricular Cardiomyocytes
journal, June 1997
- Wobus, Anna M.; Kaomei, Guan; Shan, Jin
- Journal of Molecular and Cellular Cardiology, Vol. 29, Issue 6
Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs
journal, June 2007
- Rinn, John L.; Kertesz, Michael; Wang, Jordon K.
- Cell, Vol. 129, Issue 7
Long Noncoding RNAs with Enhancer-like Function in Human Cells
journal, October 2010
- Ørom, Ulf Andersson; Derrien, Thomas; Beringer, Malte
- Cell, Vol. 143, Issue 1
A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?
journal, August 2011
- Salmena, Leonardo; Poliseno, Laura; Tay, Yvonne
- Cell, Vol. 146, Issue 3
A Transcription Factor Collective Defines Cardiac Cell Fate and Reflects Lineage History
journal, February 2012
- Junion, Guillaume; Spivakov, Mikhail; Girardot, Charles
- Cell, Vol. 148, Issue 3
Dynamic and Coordinated Epigenetic Regulation of Developmental Transitions in the Cardiac Lineage
journal, September 2012
- Wamstad, Joseph A.; Alexander, Jeffrey M.; Truty, Rebecca M.
- Cell, Vol. 151, Issue 1
Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment
journal, January 2013
- Klattenhoff, Carla A.; Scheuermann, Johanna C.; Surface, Lauren E.
- Cell, Vol. 152, Issue 3
The Tissue-Specific lncRNA Fendrr Is an Essential Regulator of Heart and Body Wall Development in the Mouse
journal, January 2013
- Grote, Phillip; Wittler, Lars; Hendrix, David
- Developmental Cell, Vol. 24, Issue 2
RNA traffic control of chromatin complexes
journal, April 2010
- Koziol, Magdalena J.; Rinn, John L.
- Current Opinion in Genetics & Development, Vol. 20, Issue 2
Widespread transcription at neuronal activity-regulated enhancers
journal, April 2010
- Kim, Tae-Kyung; Hemberg, Martin; Gray, Jesse M.
- Nature, Vol. 465, Issue 7295
lincRNAs act in the circuitry controlling pluripotency and differentiation
journal, August 2011
- Guttman, Mitchell; Donaghey, Julie; Carey, Bryce W.
- Nature, Vol. 477, Issue 7364
The T-box transcription factor Eomesodermin acts upstream of Mesp1 to specify cardiac mesoderm during mouse gastrulation
journal, August 2011
- Costello, Ita; Pimeisl, Inga-Marie; Dräger, Sarah
- Nature Cell Biology, Vol. 13, Issue 9
Non-coding RNAs as regulators of embryogenesis
journal, January 2011
- Pauli, Andrea; Rinn, John L.; Schier, Alexander F.
- Nature Reviews Genetics, Vol. 12, Issue 2
Genome-wide analysis of histone marks identifying an epigenetic signature of promoters and enhancers underlying cardiac hypertrophy
journal, November 2013
- Papait, R.; Cattaneo, P.; Kunderfranco, P.
- Proceedings of the National Academy of Sciences, Vol. 110, Issue 50
Long-Range Control of Gene Expression: Emerging Mechanisms and Disruption in Disease
journal, January 2005
- Kleinjan, Dirk A.; van Heyningen, Veronica
- The American Journal of Human Genetics, Vol. 76, Issue 1
Intergenic transcription and transinduction of the human beta -globin locus
journal, October 1997
- Ashe, H. L.; Monks, J.; Wijgerde, M.
- Genes & Development, Vol. 11, Issue 19
Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses
journal, September 2011
- Cabili, M. N.; Trapnell, C.; Goff, L.
- Genes & Development, Vol. 25, Issue 18
Chromosome 9p21 and Cardiovascular Disease: The Story Unfolds
journal, December 2008
- Samani, Nilesh J.; Schunkert, Heribert
- Circulation: Cardiovascular Genetics, Vol. 1, Issue 2
Mature Cardiomyocytes Recall Their Progenitor Experience Via Polycomb Repressive Complex 2
journal, July 2012
- He, Aibin; Pu, William T.
- Circulation Research, Vol. 111, Issue 2
Differentiation of Beating Cardiac Muscle Cells from a Derivative of P19 Embryonal Carcinoma Cells.
journal, January 1996
- Habara-Ohkubo, Akemi
- Cell Structure and Function, Vol. 21, Issue 2
Works referencing / citing this record:
Dynamics of Cardiomyocyte Transcriptome and Chromatin Landscape Demarcates Key Events of Heart Development
posted_content, December 2018
- Pawlak, Michal; Kedzierska, Katarzyna Z.; Migdal, Maciej
- bioRxiv
The long non-coding road to endogenous cardiac regeneration
journal, March 2019
- Afify, Abdel Rahman Yousry
- Heart Failure Reviews, Vol. 24, Issue 4
The long noncoding RNA Wisper controls cardiac fibrosis and remodeling
journal, June 2017
- Micheletti, Rudi; Plaisance, Isabelle; Abraham, Brian J.
- Science Translational Medicine, Vol. 9, Issue 395
Roles of long non-coding RNAs in gastric cancer metastasis
journal, January 2015
- Yang, Zi-Guo
- World Journal of Gastroenterology, Vol. 21, Issue 17
Promoter interactome of human embryonic stem cell-derived cardiomyocytes connects GWAS regions to cardiac gene networks
journal, June 2018
- Choy, Mun-Kit; Javierre, Biola M.; Williams, Simon G.
- Nature Communications, Vol. 9, Issue 1
Circulating Long Noncoding RNA UCA1 as a Novel Biomarker of Acute Myocardial Infarction
journal, January 2016
- Yan, Youyou; Zhang, Bin; Liu, Ning
- BioMed Research International, Vol. 2016
Clinical value of non-coding RNAs in cardiovascular, pulmonary, and muscle diseases
journal, January 2020
- Bonnet, Sébastien; Boucherat, Olivier; Paulin, Roxane
- American Journal of Physiology-Cell Physiology, Vol. 318, Issue 1
Long noncoding RNA in cardiac aging and disease
journal, June 2019
- Lozano-Vidal, Noelia; Bink, Diewertje I.; Boon, Reinier A.
- Journal of Molecular Cell Biology, Vol. 11, Issue 10
Concise Review: Genetic and Epigenetic Regulation of Cardiac Differentiation from Human Pluripotent Stem Cells: Molecular Mechanisms of Cardiac Differentiation
journal, May 2019
- Fujita, Jun; Tohyama, Shugo; Kishino, Yoshikazu
- STEM CELLS, Vol. 37, Issue 8
Mechanisms of long noncoding RNA function in development and disease
journal, March 2016
- Schmitz, Sandra U.; Grote, Phillip; Herrmann, Bernhard G.
- Cellular and Molecular Life Sciences, Vol. 73, Issue 13
A transcribed enhancer dictates mesendoderm specification in pluripotency
journal, November 2017
- Alexanian, Michael; Maric, Daniel; Jenkinson, Stephen P.
- Nature Communications, Vol. 8, Issue 1
The Functions of Long Non-Coding RNA during Embryonic Cardiovascular Development and Its Potential for Diagnosis and Treatment of Congenital Heart Disease
journal, June 2019
- Turton, Nadia; Swan, Ross; Mahenthiralingam, Thanujan
- Journal of Cardiovascular Development and Disease, Vol. 6, Issue 2
Long noncoding RNA Braveheart promotes cardiogenic differentiation of mesenchymal stem cells in vitro
journal, January 2017
- Hou, Jingying; Long, Huibao; Zhou, Changqing
- Stem Cell Research & Therapy, Vol. 8, Issue 1
Besides Pathology: Long Non-Coding RNA in Cell and Tissue Homeostasis
journal, January 2018
- Salviano-Silva, Amanda; Lobo-Alves, Sara; Almeida, Rodrigo
- Non-Coding RNA, Vol. 4, Issue 1
Targeting transcriptional machinery to inhibit enhancer-driven gene expression in heart failure
journal, April 2019
- Minerath, Rachel A.; Hall, Duane D.; Grueter, Chad E.
- Heart Failure Reviews, Vol. 24, Issue 5
Non-coding RNAs and exercise: pathophysiological role and clinical application in the cardiovascular system
journal, May 2018
- Gomes, Clarissa P. C.; de Gonzalo-Calvo, David; Toro, Rocio
- Clinical Science, Vol. 132, Issue 9
Long Noncoding RNA Regulation of Pluripotency
journal, January 2016
- Rosa, Alessandro; Ballarino, Monica
- Stem Cells International, Vol. 2016
Enhancer RNAs in cancer: regulation, mechanisms and therapeutic potential
journal, January 2020
- Lee, Joo-Hyung; Xiong, Feng; Li, Wenbo
- RNA Biology, Vol. 17, Issue 11
Genome-wide characterization of lncRNAs in acute myeloid leukemia
journal, February 2017
- Lei, Lijun; Xia, Siyu; Liu, Dan
- Briefings in Bioinformatics, Vol. 19, Issue 4
Regulation of angiotensin II actions by enhancers and super-enhancers in vascular smooth muscle cells
journal, November 2017
- Das, Sadhan; Senapati, Parijat; Chen, Zhuo
- Nature Communications, Vol. 8, Issue 1
Non-coding RNAs in cardiovascular diseases: diagnostic and therapeutic perspectives
journal, April 2017
- Poller, Wolfgang; Dimmeler, Stefanie; Heymans, Stephane
- European Heart Journal, Vol. 39, Issue 29
Long Noncoding RNAs in Cardiovascular Pathology, Diagnosis, and Therapy
journal, November 2016
- Bär, Christian; Chatterjee, Shambhabi; Thum, Thomas
- Circulation, Vol. 134, Issue 19
The prognostic value of matrix metalloproteinase‐7 and matrix metalloproteinase‐15 in acute myeloid leukemia
journal, December 2018
- Wu, Yingjie; Pan, Shan; Leng, Jun
- Journal of Cellular Biochemistry, Vol. 120, Issue 6
Long Noncoding RNA MHRT Protects Cardiomyocytes against H2O2-Induced Apoptosis
journal, January 2016
- Zhang, Jianying; Gao, Caihua; Meng, Meijuan
- Biomolecules & Therapeutics, Vol. 24, Issue 1
The Long Noncoding RNA Landscape of the Ischemic Human Left Ventricle
journal, January 2017
- Saddic, Louis A.; Sigurdsson, Martin I.; Chang, Tzuu-Wang
- Circulation: Cardiovascular Genetics, Vol. 10, Issue 1
Long Noncoding RNAs in Cardiovascular Diseases
journal, February 2015
- Uchida, Shizuka; Dimmeler, Stefanie
- Circulation Research, Vol. 116, Issue 4
Long noncoding RNA Meg3 regulates cardiomyocyte apoptosis in myocardial infarction
journal, October 2018
- Wu, Hongchun; Zhao, Zhen-Ao; Liu, Junwei
- Gene Therapy, Vol. 25, Issue 8
Long non-coding RNAs (lncRNAs) in skeletal and cardiac muscle: potential therapeutic and diagnostic targets?
journal, November 2016
- McMullen, Julie R.; Drew, Brian G.
- Clinical Science, Vol. 130, Issue 24
Long noncoding RNAs in kidney and cardiovascular diseases
journal, May 2016
- Lorenzen, Johan M.; Thum, Thomas
- Nature Reviews Nephrology, Vol. 12, Issue 6
Decoding the Heart through Next Generation Sequencing Approaches
journal, June 2018
- Pawlak, Michal; Niescierowicz, Katarzyna; Winata, Cecilia Lanny
- Genes, Vol. 9, Issue 6
Non-coding RNAs in muscle differentiation and musculoskeletal disease
journal, June 2016
- Ballarino, Monica; Morlando, Mariangela; Fatica, Alessandro
- Journal of Clinical Investigation, Vol. 126, Issue 6
Transcriptional control by enhancers and enhancer RNAs
journal, October 2019
- Lewis, Michael W.; Li, Shen; Franco, Hector L.
- Transcription, Vol. 10, Issue 4-5
Long non-coding RNA in stem cell pluripotency and lineage commitment: functions and evolutionary conservation
journal, January 2019
- Fico, Annalisa; Fiorenzano, Alessandro; Pascale, Emilia
- Cellular and Molecular Life Sciences, Vol. 76, Issue 8
Epigenetic modifications and noncoding RNAs in cardiac hypertrophy and failure
journal, May 2015
- Greco, Carolina M.; Condorelli, Gianluigi
- Nature Reviews Cardiology, Vol. 12, Issue 8
Enhancers as non-coding RNA transcription units: recent insights and future perspectives
journal, March 2016
- Li, Wenbo; Notani, Dimple; Rosenfeld, Michael G.
- Nature Reviews Genetics, Vol. 17, Issue 4
Dynamics of cardiomyocyte transcriptome and chromatin landscape demarcates key events of heart development
journal, February 2019
- Pawlak, Michal; Kedzierska, Katarzyna Z.; Migdal, Maciej
- Genome Research, Vol. 29, Issue 3
Promoter interactome of human embryonic stem cell-derived cardiomyocytes connects GWAS regions to cardiac gene networks.
text, January 2018
- Choy, Mun-Kit; Javierre, Biola M.; Williams, Simon G.
- Apollo - University of Cambridge Repository
A transcribed enhancer dictates mesendoderm specification in pluripotency
text, January 2017
- Alexanian, Michael; Maric, Daniel; Jenkinson, Stephen Philip
- Nature Publishing Group
Mechanisms of long noncoding RNA function in development and disease
journal, March 2016
- Schmitz, Sandra U.; Grote, Phillip; Herrmann, Bernhard G.
- Cellular and Molecular Life Sciences, Vol. 73, Issue 13
Cardiomyocyte Lineage Specification in Adult Human Cardiac Precursor Cells Via Modulation of Enhancer-Associated Long Noncoding RNA Expression
journal, October 2016
- Plaisance, Isabelle; Perruchoud, Stéphanie; Fernandez-Tenorio, Miguel
- JACC: Basic to Translational Science, Vol. 1, Issue 6
Non-coding microRNAs for cardiac regeneration: Exploring novel alternatives to induce heart healing
journal, June 2017
- Garreta, Elena; Prado, Patricia; Izpisua Belmonte, Juan Carlos
- Non-coding RNA Research, Vol. 2, Issue 2
The promise of enhancer-associated long noncoding RNAs in cardiac regeneration
journal, October 2015
- Ounzain, Samir; Pedrazzini, Thierry
- Trends in Cardiovascular Medicine, Vol. 25, Issue 7
Discovery and functional characterization of cardiovascular long noncoding RNAs
journal, December 2015
- Ounzain, Samir; Burdet, Frédéric; Ibberson, Mark
- Journal of Molecular and Cellular Cardiology, Vol. 89
Author Correction: Promoter interactome of human embryonic stem cell-derived cardiomyocytes connects GWAS regions to cardiac gene networks
journal, November 2018
- Choy, Mun-Kit; Javierre, Biola M.; Williams, Simon G.
- Nature Communications, Vol. 9, Issue 1
Transcriptional control by enhancers and enhancer RNAs
journal, October 2019
- Lewis, Michael W.; Li, Shen; Franco, Hector L.
- Transcription, Vol. 10, Issue 4-5
Long noncoding RNA in cardiac aging and disease
journal, June 2019
- Lozano-Vidal, Noelia; Bink, Diewertje I.; Boon, Reinier A.
- Journal of Molecular Cell Biology, Vol. 11, Issue 10
Long Noncoding RNA Regulation of Pluripotency
journal, January 2016
- Rosa, Alessandro; Ballarino, Monica
- Stem Cells International, Vol. 2016
Circulating Long Noncoding RNA UCA1 as a Novel Biomarker of Acute Myocardial Infarction
journal, January 2016
- Yan, Youyou; Zhang, Bin; Liu, Ning
- BioMed Research International, Vol. 2016
Human Long Noncoding RNA Regulation of Stem Cell Potency and Differentiation
journal, January 2017
- Lee, Seahyoung; Seo, Hyang-Hee; Lee, Chang Youn
- Stem Cells International, Vol. 2017
Long Noncoding RNAs as Inducers and Terminators of Vascular Development
journal, April 2015
- Viereck, Janika; Kumarswamy, Regalla; Thum, Thomas
- Circulation, Vol. 131, Issue 14
Inhibition of the Hypoxia-Inducible Factor 1α–Induced Cardiospecific HERNA1 Enhance-Templated RNA Protects From Heart Disease
journal, June 2019
- Mirtschink, Peter; Bischof, Corinne; Pham, Minh-Duc
- Circulation, Vol. 139, Issue 24
Long noncoding RNA Braveheart promotes cardiogenic differentiation of mesenchymal stem cells in vitro
journal, January 2017
- Hou, Jingying; Long, Huibao; Zhou, Changqing
- Stem Cell Research & Therapy, Vol. 8, Issue 1
Molecular mechanisms of long noncoding RNAs and their role in disease pathogenesis
journal, January 2018
- Hu, Guoku; Niu, Fang; Humburg, Bree A.
- Oncotarget, Vol. 9, Issue 26
It’s Time for An Epigenomics Roadmap of Heart Failure
journal, June 2015
- Papait, Roberto; Corrado, Nadia; Rusconi, Francesca
- Current Genomics, Vol. 16, Issue 4
A lncRNA Perspective into (Re)Building the Heart
journal, November 2016
- Frank, Stefan; Aguirre, Aitor; Hescheler, Juergen
- Frontiers in Cell and Developmental Biology, Vol. 4
Heart Enhancers: Development and Disease Control at a Distance
journal, March 2021
- Yuan, Xuefei; Scott, Ian C.; Wilson, Michael D.
- Frontiers in Genetics, Vol. 12
Decoding the Heart through Next Generation Sequencing Approaches
journal, June 2018
- Pawlak, Michal; Niescierowicz, Katarzyna; Winata, Cecilia Lanny
- Genes, Vol. 9, Issue 6
The Functions of Long Non-Coding RNA during Embryonic Cardiovascular Development and Its Potential for Diagnosis and Treatment of Congenital Heart Disease
journal, June 2019
- Turton, Nadia; Swan, Ross; Mahenthiralingam, Thanujan
- Journal of Cardiovascular Development and Disease, Vol. 6, Issue 2
Besides Pathology: Long Non-Coding RNA in Cell and Tissue Homeostasis
journal, January 2018
- Salviano-Silva, Amanda; Lobo-Alves, Sara; Almeida, Rodrigo
- Non-Coding RNA, Vol. 4, Issue 1
Long Noncoding RNA MHRT Protects Cardiomyocytes against H2O2-Induced Apoptosis
journal, January 2016
- Zhang, Jianying; Gao, Caihua; Meng, Meijuan
- Biomolecules & Therapeutics, Vol. 24, Issue 1
Genome-wide interaction target profiling reveals a novel Peblr20-eRNA activation pathway to control stem cell pluripotency
journal, January 2020
- Wang, Cong; Jia, Lin; Wang, Yichen
- Theranostics, Vol. 10, Issue 1
A transcribed enhancer dictates mesendoderm specification in pluripotency
text, January 2017
- Alexanian, Michael; Maric, Daniel; Jenkinson, Stephen Philip
- Nature Publishing Group