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 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 Myocyte Enhancer Factor 2 and Chorion Factor 2 Collaborate in Activation of the Myogenic Program in Drosophila

2007 ◽  
Vol 28 (5) ◽  
pp. 1616-1629 ◽  
Author(s):  
Kathleen K. Kelly Tanaka ◽  
Anton L. Bryantsev ◽  
Richard M. Cripps
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Control Cell ◽  
Actin Gene ◽  
Myocyte Enhancer Factor 2 ◽  
Myocyte Enhancer Factor ◽  
General Importance ◽  
Myogenic Program ◽  
Enhancer Factor

ABSTRACT The process of myogenesis requires the coordinated activation of many structural genes whose products are required for myofibril assembly, function, and regulation. Although numerous reports have documented the importance of the myogenic regulator myocyte enhancer factor 2 (MEF2) in muscle differentiation, the interaction of MEF2 with cofactors is critical to the realization of muscle fate. We identify here a genomic region required for full MEF2-mediated activation of actin gene expression in Drosophila, and we identify the zinc finger transcriptional regulator chorion factor 2 (CF2) as a factor functioning alongside MEF2 via this region. Furthermore, although both MEF2 and CF2 can individually activate actin gene expression, we demonstrate that these two factors collaborate in regulating the Actin57B target gene in vitro and in vivo. More globally, MEF2 and CF2 synergistically activate the enhancers of a number of muscle-specific genes, and loss of CF2 function in vivo results in reductions in the levels of several muscle structural gene transcripts. These findings validate a general importance of CF2 alongside MEF2 as a critical regulator of the myogenic program, identify a new regulator functioning with MEF2 to control cell fate, and provide insight into the network of regulatory events that shape the developing musculature.

scholarly journals Myocyte Enhancer Factor 2 Acetylation by p300 Enhances Its DNA Binding Activity, Transcriptional Activity, and Myogenic Differentiation

2005 ◽  
Vol 25 (9) ◽  
pp. 3575-3582 ◽  
Author(s):  
Kewei Ma ◽  
Jonathan K. L. Chan ◽  
Guang Zhu ◽  
Zhenguo Wu
Keyword(s):  
Dna Binding ◽  
Transcriptional Activity ◽  
Myogenic Differentiation ◽  
Binding Activity ◽  
Transactivation Domain ◽  
Myocyte Enhancer Factor 2 ◽  
Myocyte Enhancer Factor ◽  
Enhancer Factor

ABSTRACT Myocyte enhancer factor 2 (MEF2) family proteins are key transcription factors controlling gene expression in myocytes, lymphocytes, and neurons. MEF2 proteins are known to be regulated by phosphorylation. We now provide evidence showing that MEF2C is acetylated by p300 both in vitro and in vivo. In C2C12 myogenic cells, MEF2 is preferentially acetylated in differentiating myocytes but not in undifferentiated myoblasts. Several major acetylation sites are mapped to the transactivation domain of MEF2C, some of which are fully conserved in other MEF2 members from several different species. Mutation of these lysines affects MEF2 DNA binding and transcriptional activity, as well as its synergistic effect with myogenin in myogenic conversion assays. When introduced into C2C12 myoblasts, the nonacetylatable MEF2C inhibits myogenic differentiation. Thus, in addition to phosphorylation, MEF2 activity is also critically regulated by acetylation during myogenesis.

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 Epstein-Barr Virus Nuclear Antigen 3C Interacts with Histone Deacetylase To Repress Transcription

1999 ◽  
Vol 73 (7) ◽  
pp. 5688-5697 ◽  
Author(s):  
Stoyan A. Radkov ◽  
Robert Touitou ◽  
Alex Brehm ◽  
Martin Rowe ◽  
Michelle West ◽  
...  
Keyword(s):  
Dna Binding ◽  
Histone Deacetylase ◽  
Mutational Analysis ◽  
Binding Protein ◽  
Trichostatin A ◽  
Nuclear Antigen ◽  
Physical Interaction ◽  
Bacterial Cells ◽  
Histone Deacetylase 1

ABSTRACT EBNA3C can specifically repress the expression of reporter plasmids containing EBV Cp latency-associated promoter elements. Cp is normally the main promoter for EBNA mRNA initiation, so it appears that EBNA3C contributes to a negative autoregulatory control loop. By mutational analysis it was previously established that this repression is consistent with EBNA3C being targeted to Cp by binding the cellular sequence-specific DNA-binding protein CBF1 (also known as recombination signal-binding protein [RBP]-Jκ. Further analysis suggested that in vivo a corepressor interacts with EBNA3C in this DNA binding complex. Results presented here are all consistent with a component of such a corepressor exhibiting histone deacetylase activity. The drug trichostatin A, which specifically inhibits histone deacetylases, relieved two- to threefold the repression of Cp induced by EBNA3C in two different cell types. Moreover, repression of pTK-CAT-Cp4× by EBNA3C was specifically enhanced by cotransfection of an expression plasmid for human histone deacetylase-1 (HDAC1). Consistent with these functional assays, in vitro-translated HDAC1 bound to a glutathioneS-transferase (GST) fusion protein including full-length EBNA3C, and in the reciprocal experiment EBNA3C bound to a GST fusion with the N terminus of HDAC1. Coimmunoprecipitations also revealed an EBNA3C-HDAC1 interaction in vivo, and GST-EBNA3C bound functional histone deacetylase enzyme activity from HeLa cell nuclear extracts. The region of EBNA3C involved in the interaction with HDAC1 appears to correspond to the region which is necessary for binding to CBF1/RBP-Jκ. A direct physical interaction between EBNA3C and HDAC1 was demonstrated with recombinant proteins purified from bacterial cells, and we therefore conclude that HDAC1 and CBF1/RBP-Jκ bind to the same or adjacent regions of EBNA3C. These data suggest that recruitment of histone deacetylase activity makes a significant contribution to the repression of transcription from Cp because EBNA3C bridges an interaction between CBF1/RBP-Jκ and HDAC1.

scholarly journals Targeted Deletion of mek5 Causes Early Embryonic Death and Defects in the Extracellular Signal-Regulated Kinase 5/Myocyte Enhancer Factor 2 Cell Survival Pathway

2005 ◽  
Vol 25 (1) ◽  
pp. 336-345 ◽  
Author(s):  
Xin Wang ◽  
Anita J. Merritt ◽  
Jan Seyfried ◽  
Chun Guo ◽  
Emmanouil S. Papadakis ◽  
...  
Keyword(s):  
Cell Survival ◽  
Cell Cycle Progression ◽  
Cardiac Development ◽  
Myocyte Enhancer Factor 2 ◽  
Targeted Deletion ◽  
Extracellular Signal Regulated Kinase ◽  
Myocyte Enhancer Factor ◽  
Extracellular Signal ◽  
Enhancer Factor

ABSTRACT To elucidate the physiological significance of MEK5 in vivo, we have examined the effect of mek5 gene elimination in mice. Heterozygous mice appear to be healthy and were fertile. However, mek5 − / − embryos die at approximately embryonic day 10.5 (E10.5). The phenotype of the mek5 − / − embryos includes abnormal cardiac development as well as a marked decrease in proliferation and an increase in apoptosis in the heart, head, and dorsal regions of the mutant embryos. The absence of MEK5 does not affect cell cycle progression but sensitizes mouse embryonic fibroblasts (MEFs) to the ability of sorbitol to enhance caspase 3 activity. Further studies with mek5 − / − MEFs indicate that MEK5 is required for mediating extracellular signal-regulated kinase 5 (ERK5) activation and for the regulation of the transcriptional activity of myocyte enhancer factor 2. Overall, this is the first study to rigorously establish the role of MEK5 in vivo as an activator of ERK5 and as an essential regulator of cell survival that is required for normal embryonic development.

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