共 45 条
HDAC4 controls histone methylation in response to elevated cardiac load
被引:168
作者:

Hohl, Mathias
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机构:
Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany

Wagner, Michael
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Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany

Reil, Jan-Christian
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Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany

Mueller, Sarah-Anne
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Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany

Tauchnitz, Marcus
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Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany

Zimmer, Angela M.
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Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany

Lehmann, Lorenz H.
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机构:
Univ Klinikum Heidelberg, Innere Med Klin 3, Heidelberg, Germany
German Ctr Cardiovasc Res DZHK, Heidelberg, Germany Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany

Thiel, Gerald
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Univ Klinikum Saarlandes, D-66421 Homburg, Germany Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany

Boehm, Michael
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Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany

Backs, Johannes
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机构:
Univ Klinikum Heidelberg, Innere Med Klin 3, Heidelberg, Germany
German Ctr Cardiovasc Res DZHK, Heidelberg, Germany Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany

Maack, Christoph
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Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany
机构:
[1] Univ Klinikum Saarlandes, Innere Med Klin 3, D-66421 Homburg, Germany
[2] Univ Klinikum Heidelberg, Innere Med Klin 3, Heidelberg, Germany
[3] German Ctr Cardiovasc Res DZHK, Heidelberg, Germany
[4] Univ Klinikum Saarlandes, D-66421 Homburg, Germany
关键词:
CAM KINASE-II;
GENE-EXPRESSION;
LYSINE;
9;
TRANSCRIPTION;
H3;
DEACETYLASES;
HYPERTROPHY;
DEMETHYLASE;
HEART;
ASSOCIATION;
D O I:
10.1172/JCI61084
中图分类号:
R-3 [医学研究方法];
R3 [基础医学];
学科分类号:
1001 ;
摘要:
In patients with heart failure, reactivation of a fetal gene program, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), is a hallmark for maladaptive remodeling of the LV. The mechanisms that regulate this reactivation are incompletely understood. Histone acetylation and methylation affect the conformation of chromatin, which in turn governs the accessibility of DNA for transcription factors. Using human LV myocardium, we found that, despite nuclear export of histone deacetylase 4 (HDAC4), upregulation of ANP and BNP in failing hearts did not require increased histone acetylation in the promoter regions of these genes. In contrast, di- and trimethylation of lysine 9 of histone 3 (H3K9) and binding of heterochromatin protein 1 (HP1) in the promoter regions of these genes were substantially reduced. In isolated working murine hearts, an acute increase of cardiac preload induced HDAC4 nuclear export, H3K9 demethylation, HP1 dissociation from the promoter region, and activation of the ANP gene. These processes were reversed in hearts with myocyte-specific deletion of Hdac4. We conclude that HDAC4 plays a central role for rapid modifications of histone methylation in response to variations in cardiac load and may represent a target for pharmacological interventions to prevent maladaptive remodeling in patients with heart failure.
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收藏
页码:1359 / 1370
页数:12
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JDRF, Int Ctr Diabet Complicat Res, Albert Einstein Coll Med, Bronx, NY USA Baker IDI Heart & Diabet Inst, Epigenet Human Hlth & Dis Lab, Melbourne, Vic, Australia

Cooper, Mark E.
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机构:
JDRF, Baker IDI Heart & Diabet Inst, Danielle Alberti Ctr Diabet Complicat, Diabet Div, Melbourne, Vic, Australia
JDRF, Int Ctr Diabet Complicat Res, Albert Einstein Coll Med, Bronx, NY USA Baker IDI Heart & Diabet Inst, Epigenet Human Hlth & Dis Lab, Melbourne, Vic, Australia

El-Osta, Assam
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h-index: 0
机构:
Baker IDI Heart & Diabet Inst, Epigenet Human Hlth & Dis Lab, Melbourne, Vic, Australia Baker IDI Heart & Diabet Inst, Epigenet Human Hlth & Dis Lab, Melbourne, Vic, Australia