scholarly journals Calcium Regulates Transcriptional Repression of Myocyte Enhancer Factor 2 by Histone Deacetylase 4

2000 ◽  
Vol 275 (29) ◽  
pp. 22563-22567 ◽  
Author(s):  
Hong-Duk Youn ◽  
Christina M. Grozinger ◽  
Jun O. Liu
Keyword(s):  
Histone Deacetylase ◽  
Transcriptional Repression ◽  
Myocyte Enhancer Factor 2 ◽  
Myocyte Enhancer Factor ◽  
Histone Deacetylase 4 ◽  
Enhancer Factor

scholarly journals Direct Interaction of Ca2+/Calmodulin Inhibits Histone Deacetylase 5 Repressor Core Binding to Myocyte Enhancer Factor 2

2003 ◽  
Vol 278 (20) ◽  
pp. 17625-17635 ◽  
Author(s):  
Imre Berger ◽  
Christoph Bieniossek ◽  
Christiane Schaffitzel ◽  
Markus Hassler ◽  
Eugenio Santelli ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Direct Interaction ◽  
Myocyte Enhancer Factor 2 ◽  
Myocyte Enhancer Factor ◽  
Enhancer Factor

scholarly journals Histone Deacetylase 3 Interacts with and Deacetylates Myocyte Enhancer Factor 2

2006 ◽  
Vol 27 (4) ◽  
pp. 1280-1295 ◽  
Author(s):  
Serge Grégoire ◽  
Lin Xiao ◽  
Jianyun Nie ◽  
Xiaohong Zhang ◽  
Minghong Xu ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Thyroid Hormone Receptor ◽  
Trichostatin A ◽  
Hek293 Cells ◽  
Physical Interaction ◽  
Myocyte Enhancer Factor 2 ◽  
Specific Domain ◽  
Myocyte Enhancer Factor ◽  
Enhancer Factor

ABSTRACT The myocyte enhancer factor 2 (MEF2) family of transcription factors is not only important for controlling gene expression in normal cellular programs, like muscle differentiation, T-cell apoptosis, neuronal survival, and synaptic differentiation, but has also been linked to cardiac hypertrophy and other pathological conditions. Lysine acetylation has been shown to modulate MEF2 function, but it is not so clear which deacetylase(s) is involved. We report here that treatment of HEK293 cells with trichostatin A or nicotinamide upregulated MEF2D acetylation, suggesting that different deacetylases catalyze the deacetylation. Related to the trichostatin A sensitivity, histone deacetylase 4 (HDAC4) and HDAC5, two known partners of MEF2, exhibited little deacetylase activity towards MEF2D. In contrast, HDAC3 efficiently deacetylated MEF2D in vitro and in vivo. This was specific, since HDAC1, HDAC2, and HDAC8 failed to do so. While HDAC4, HDAC5, HDAC7, and HDAC9 are known to recognize primarily the MEF2-specific domain, we found that HDAC3 interacts directly with the MADS box. In addition, HDAC3 associated with the acetyltransferases p300 and p300/CBP-associated factor (PCAF) to reverse autoacetylation. Furthermore, the nuclear receptor corepressor SMRT (silencing mediator of retinoid acid and thyroid hormone receptor) stimulated the deacetylase activity of HDAC3 towards MEF2 and PCAF. Supporting the physical interaction and deacetylase activity, HDAC3 repressed MEF2-dependent transcription and inhibited myogenesis. These results reveal an unexpected role for HDAC3 and suggest a novel pathway through which MEF2 activity is controlled in vivo.

scholarly journals α-Actinin 4 Potentiates Myocyte Enhancer Factor-2 Transcription Activity by Antagonizing Histone Deacetylase 7

2006 ◽  
Vol 281 (46) ◽  
pp. 35070-35080 ◽  
Author(s):  
Sharmistha Chakraborty ◽  
Erin L. Reineke ◽  
Minh Lam ◽  
Xiaofang Li ◽  
Yu Liu ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Myocyte Enhancer Factor 2 ◽  
Transcription Activity ◽  
Myocyte Enhancer Factor ◽  
Enhancer Factor

scholarly journals Structural and functional cardiac profile after prolonged duration of mechanical unloading: potential implications for myocardial recovery

2018 ◽  
Vol 315 (5) ◽  
pp. H1463-H1476 ◽  
Author(s):  
Estibaliz Castillero ◽  
Ziad A. Ali ◽  
Hirokazu Akashi ◽  
Nicholas Giangreco ◽  
Catherine Wang ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Structural Protein ◽  
Myocyte Enhancer Factor 2 ◽  
Ventricular Assist ◽  
Myocyte Enhancer Factor ◽  
Left Ventricular Assist ◽  
Histone Deacetylase 4 ◽  
Dependent Protein ◽  
Lvad Support ◽  
Enhancer Factor

Clinical and experimental studies have suggested that the duration of left ventricular assist device (LVAD) support may affect remodeling of the failing heart. We aimed to 1) characterize the changes in Ca2+/calmodulin-dependent protein kinase type-IIδ (CaMKIIδ), growth signaling, structural proteins, fibrosis, apoptosis, and gene expression before and after LVAD support and 2) assess whether the duration of support correlated with improvement or worsening of reverse remodeling. Left ventricular apex tissue and serum pairs were collected in patients with dilated cardiomyopathy ( n = 25, 23 men and 2 women) at LVAD implantation and after LVAD support at cardiac transplantation/LVAD explantation. Normal cardiac tissue was obtained from healthy hearts ( n = 4) and normal serum from age-matched control hearts ( n = 4). The duration of LVAD support ranged from 48 to 1,170 days (median duration: 270 days). LVAD support was associated with CaMKIIδ activation, increased nuclear myocyte enhancer factor 2, sustained histone deacetylase-4 phosphorylation, increased circulating and cardiac myostatin (MSTN) and MSTN signaling mediated by SMAD2, ongoing structural protein dysregulation and sustained fibrosis and apoptosis (all P < 0.05). Increased CaMKIIδ phosphorylation, nuclear myocyte enhancer factor 2, and cardiac MSTN significantly correlated with the duration of support. Phosphorylation of SMAD2 and apoptosis decreased with a shorter duration of LVAD support but increased with a longer duration of LVAD support. Further study is needed to define the optimal duration of LVAD support in patients with dilated cardiomyopathy. NEW & NOTEWORTHY A long duration of left ventricular assist device support may be detrimental for myocardial recovery, based on myocardial tissue experiments in patients with prolonged support showing significantly worsened activation of Ca2+/calmodulin-dependent protein kinase-IIδ, increased nuclear myocyte enhancer factor 2, increased myostatin and its signaling by SMAD2, and apoptosis as well as sustained histone deacetylase-4 phosphorylation, structural protein dysregulation, and fibrosis.

scholarly journals AMP-activated Protein Kinase Regulates β-Catenin Transcription via Histone Deacetylase 5

2011 ◽  
Vol 286 (18) ◽  
pp. 16426-16434 ◽  
Author(s):  
Jun-Xing Zhao ◽  
Wan-Fu Yue ◽  
Mei-Jun Zhu ◽  
Min Du
Keyword(s):  
Cell Differentiation ◽  
Protein Kinase ◽  
Mrna Expression ◽  
Histone Deacetylase ◽  
Myocyte Enhancer Factor 2 ◽  
Myocyte Enhancer Factor ◽  
Ampk Activity ◽  
Underlying Mechanisms ◽  
Amp Activated Protein Kinase ◽  
Enhancer Factor

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism; it is inhibited under obese conditions and is activated by exercise and by many anti-diabetic drugs. Emerging evidence also suggests that AMPK regulates cell differentiation, but the underlying mechanisms are unclear. We hypothesized that AMPK regulates cell differentiation via altering β-catenin expression, which involves phosphorylation of class IIa histone deacetylase 5 (HDAC5). In both C3H10T1/2 cells and mouse embryonic fibroblasts (MEFs), AMPK activity was positively correlated with β-catenin content. Chemical inhibition of HDAC5 increased β-catenin mRNA expression. HDAC5 overexpression reduced and HDAC5 knockdown increased H3K9 acetylation and cellular β-catenin content. HDAC5 formed a complex with myocyte enhancer factor-2 to down-regulate β-catenin mRNA expression. AMPK phosphorylated HDAC5, which promoted HDAC5 exportation from the nucleus; mutation of two phosphorylation sites in HDAC5, Ser-259 and -498, abolished the regulatory role of AMPK on β-catenin expression. In conclusion, AMPK promotes β-catenin expression through phosphorylation of HDAC5, which reduces HDAC5 interaction with the β-catenin promoter via myocyte enhancer factor-2. Thus, the data indicate that AMPK regulates cell differentiation and development via cross-talk with the wingless and Int (Wnt)/β-catenin signaling pathway.

scholarly journals PC4 Coactivates MyoD by Relieving the Histone Deacetylase 4-Mediated Inhibition of Myocyte Enhancer Factor 2C

2005 ◽  
Vol 25 (6) ◽  
pp. 2242-2259 ◽  
Author(s):  
Laura Micheli ◽  
Luca Leonardi ◽  
Filippo Conti ◽  
Pasquale Buanne ◽  
Nadia Canu ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Inhibitory Effect ◽  
Myoblast Differentiation ◽  
Gene Promoters ◽  
Amino Terminal ◽  
Myocyte Enhancer Factor ◽  
Histone Deacetylase 4 ◽  
Regulatory Loop ◽  
Muscle Gene ◽  
Enhancer Factor

ABSTRACT Histone deacetylase 4 (HDAC4) negatively regulates skeletal myogenesis by associating with the myocyte enhancer factor 2 (MEF2) transcription factors. Our data indicate that the gene PC4 (interferon-related developmental regulator 1 [IFRD1], Tis7), which we have previously shown to be required for myoblast differentiation, is both induced by MyoD and potentiates the transcriptional activity of MyoD, thus revealing a positive regulatory loop between these molecules. Enhancement by PC4 of MyoD-dependent activation of muscle gene promoters occurs selectively through MEF2 binding sites. Furthermore, PC4 localizes in the nucleus of differentiating myoblasts, associates with MEF2C, and is able to counteract the HDAC4-mediated inhibition of MEF2C. This latter action can be explained by the observed ability of PC4 to dose dependently displace HDAC4 from MEF2C. Consistently, we have observed that (i) the region of PC4 that binds MEF2C is sufficient to counteract the inhibition by HDAC4; (ii) PC4, although able to bind HDAC4, does not inhibit the enzymatic activity of HDAC4; and (iii) PC4 overcomes the inhibition mediated by the amino-terminal domain of HDAC4, which associates with MEF2C but not with PC4. Together, our findings strongly suggest that PC4 acts as a coactivator of MyoD and MEF2C by removing the inhibitory effect of HDAC4, thus exerting a pivotal function during myogenesis.

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