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Citations to this article

Cardiac hypertrophy and histone deacetylase–dependent transcriptional repression mediated by the atypical homeodomain protein Hop
Hyun Kook, … , Peter Gruber, Jonathan A. Epstein
Hyun Kook, … , Peter Gruber, Jonathan A. Epstein
Published September 15, 2003
Citation Information: J Clin Invest. 2003;112(6):863-871. https://doi.org/10.1172/JCI19137.
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Article Cardiology Article has an altmetric score of 7

Cardiac hypertrophy and histone deacetylase–dependent transcriptional repression mediated by the atypical homeodomain protein Hop

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Abstract

Activation of multiple pathways is associated with cardiac hypertrophy and heart failure. Repression of antihypertrophic pathways has rarely been demonstrated to cause cardiac hypertrophy in vivo. Hop is an unusual homeodomain protein that is expressed by embryonic and postnatal cardiac myocytes. Unlike other homeodomain proteins, Hop does not bind DNA. Rather, it modulates cardiac growth and proliferation by inhibiting the transcriptional activity of serum response factor (SRF) in cardiomyocytes. Here we show that Hop can inhibit SRF-dependent transcriptional activation by recruiting histone deacetylase (HDAC) activity and can form a complex that includes HDAC2. Transgenic mice that overexpress Hop develop severe cardiac hypertrophy, cardiac fibrosis, and premature death. A mutant form of Hop, which does not recruit HDAC activity, does not induce hypertrophy. Treatment of Hop transgenic mice with trichostatin A, an HDAC inhibitor, prevents hypertrophy. In addition, trichostatin A also attenuates hypertrophy induced by infusion of isoproterenol. Thus, chromatin remodeling and repression of otherwise active transcriptional processes can result in hypertrophy and heart failure, and this process can be blocked with chemical HDAC inhibitors.

Authors

Hyun Kook, John J. Lepore, Aaron D. Gitler, Min Min Lu, Wendy Wing-Man Yung, Joel Mackay, Rong Zhou, Victor Ferrari, Peter Gruber, Jonathan A. Epstein

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Total citations by year

Year: 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 Total
Citations: 7 2 9 6 7 8 7 6 5 11 9 12 6 11 10 8 7 4 6 3 2 1 147
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Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009
The many roles of histone deacetylases in development and physiology: implications for disease and therapy
M Haberland, RL Montgomery, EN Olson
Nature reviews. Genetics 2009
RFXB and its splice variant RFXBSV mediate the antagonism between IFN  and TGF  on COL1A2 transcription in vascular smooth muscle cells
M Fang, X Kong, P Li, F Fang, X Wu, H Bai, X Qi, Q Chen, Y Xu
Nucleic Acids Research 2009
Abrogation of TGF-beta1-induced fibroblast-myofibroblast differentiation by histone deacetylase inhibition
W Guo, B Shan, RC Klingsberg, X Qin, JA Lasky
American journal of physiology. Lung cellular and molecular physiology 2009
Identification of genes differentially expressed as result of adenovirus type 5- and adenovirus type 12-transformation
J Strath, LJ Georgopoulos, P Kellam, GE Blair
BMC Genomics 2009
Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated gene- and microRNA-expression signatures: a Cancer and Leukemia Group B study
H Becker, G Marcucci, K Maharry, MD Radmacher, K Mrózek, D Margeson, SP Whitman, YZ Wu, S Schwind, P Paschka, BL Powell, TH Carter, JE Kolitz, M Wetzler, AJ Carroll, MR Baer, MA Caligiuri, RA Larson, CD Bloomfield
Journal of Clinical Oncology 2009
Endothelin-Stimulated Human B-Type Natriuretic Peptide Gene Expression Is Mediated by Yin Yang 1 in Association With Histone Deacetylase 2
DJ Glenn, F Wang, S Chen, M Nishimoto, DG Gardner
Hypertension 2009
Curcumin Prevents and Reverses Cardiac Hypertrophy
Hong-Liang Li, Chen Liu, Geoffrey de Couto, Maral Ouzounian, Mei Sun, Ai-Bing Wang, Yue Huang, Cheng-Wei He, Yu Shi, Xin Chen, Mai P. Nghiem, Youan Liu, Manyin Chen, Fayez Dawood, Masahiro Fukuoka, Yuichiro Maekawa, Liyong Zhang, Andrew Leask, Asish K. Ghosh, Lorrie A. Kirshenbaum, Peter. P Liu
Journal of Clinical Investigation 2008
Currying favor for the heart
Jonathan A. Epstein
Journal of Clinical Investigation 2008
Glycogen synthase kinase 3 (GSK3) in the heart: a point of integration in hypertrophic signalling and a therapeutic target? A critical analysis
PH Sugden, SJ Fuller, SC Weiss, A Clerk
British Journal of Pharmacology 2008
A new (heat) shocking player in cardiac hypertrophy
TM Vondriska, Y Wang
Circulation research 2008
Epigenetic regulation of cardiac muscle-specific genes in H9c2 cells by Interleukin-18 and histone deacetylase inhibitor m-carboxycinnamic acid bis-hydroxamide
G Majumdar, IM Johnson, S Kale, R Raghow
Molecular and Cellular Biochemistry 2008
Histone-deacetylase inhibition reverses atrial arrhythmia inducibility and fibrosis in cardiac hypertrophy independent of angiotensin
F Liu, MD Levin, NB Petrenko, MM Lu, T Wang, LJ Yuan, AL Stout, JA Epstein, VV Patel
Journal of Molecular and Cellular Cardiology 2008
Transgenic Overexpression of Hdac3 in the Heart Produces Increased Postnatal Cardiac Myocyte Proliferation but Does Not Induce Hypertrophy
CM Trivedi, MM Lu, Q Wang, JA Epstein
The Journal of biological chemistry 2008
TGFbeta inducible early gene-1 (TIEG1) and cardiac hypertrophy: Discovery and characterization of a novel signaling pathway
NM Rajamannan, M Subramaniam, TP Abraham, VC Vasile, MJ Ackerman, DG Monroe, TL Chew, TC Spelsberg
Journal of Cellular Biochemistry 2007
Re-employment of developmental transcription factors in adult heart disease
T Oka, J Xu, JD Molkentin
Seminars in Cell & Developmental Biology 2007
Epigenetic abnormalities in cardiac hypertrophy and heart failure
H Mano
Environmental Health and Preventive Medicine 2007
Anticancer prodrugs of butyric acid and formaldehyde protect against doxorubicin-induced cardiotoxicity
A Rephaeli, S Waks-Yona, A Nudelman, I Tarasenko, N Tarasenko, DR Phillips, SM Cutts, G Kessler-Icekson
British Journal of Cancer 2007
Control of SRF binding to CArG-box chromatin regulates smooth muscle gene expression in vivo
Oliver G. McDonald, Brian R. Wamhoff, Mark H. Hoofnagle, Gary K. Owens
Journal of Clinical Investigation 2006
Transcription factor CHF1/Hey2 suppresses cardiac hypertrophy through an inhibitory interaction with GATA4
F Xiang, Y Sakata, L Cui, JM Youngblood, H Nakagami, JK Liao, R Liao, MT Chin
American journal of physiology. Heart and circulatory physiology 2006
Recent insights into cardiac hypertrophy and left ventricular remodeling
R Kerkela, T Force
Current Heart Failure Reports 2006
Role of homeodomain-only protein in the cardiac conduction system
F Liu, FA Ismat, VV Patel
Trends in Cardiovascular Medicine 2006
Suppression of Class I and II Histone Deacetylases Blunts Pressure-Overload Cardiac Hypertrophy
Y Kong, P Tannous, G Lu, K Berenji, BA Rothermel, EN Olson, JA Hill
Circulation 2006
Changes in skeletal muscle gene expression following clenbuterol administration
DM Spurlock, TG McDaneld, LM McIntyre
BMC Genomics 2006
Genetic causes of human heart failure
H Morita, J Seidman, CE Seidman
Journal of Clinical Investigation 2005
Toward transcriptional therapies for the failing heart: chemical screens to modulate genes
TA McKinsey, EN Olson
Journal of Clinical Investigation 2005
Homeobox Protein Hop Functions in the Adult Cardiac Conduction System
FA Ismat, M Zhang, H Kook, B Huang, R Zhou, VA Ferrari, JA Epstein, VV Patel
Circulation research 2005
Histone deacetylases 5 and 9 govern responsiveness of the heart to a subset of stress signals and play redundant roles in heart development
S Chang, TA McKinsey, CL Zhang, JA Richardson, JA Hill, EN Olson
Molecular and cellular biology 2004
Muscle ring finger protein-1 inhibits PKCε activation and prevents cardiomyocyte hypertrophy
R Arya, V Kedar, JR Hwang, H McDonough, HH Li, J Taylor, C Patterson
The Journal of Cell Biology 2004
HATs off to Hop: recruitment of a class I histone deacetylase incriminates a novel transcriptional pathway that opposes cardiac hypertrophy
Y Hamamori, MD Schneider
Journal of Clinical Investigation 2003

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