Myocyte enhancer factor 2 (MEF2) transcription factors play pivotal roles in striated muscle, neuron, and lymphocyte gene expression and are targets of stress- and calcium-mediated signaling. All MEF2 gene products have a common DNA binding and dimerization domain, but MEF2 transcripts are alternatively spliced among coding exons to produce splicing isoforms. In vertebrate MEF2A, -C, and -D, a ...

Class II histone deacetylases (HDACs) bind myocyte enhancer factor-2 (MEF2) and repress specific gene expression in a calcium-dependent manner. Despite their significant physiological functions in muscle, immune and neuronal cells, the mechanism of recruitment of class II HDACs by MEF2 is not well understood. Here, we have characterized the complex between the MEF2-binding motif of class II HDA...

The transcription factor Mef2 has well established roles in muscle development in Drosophila and in the differentiation of many cell types in mammals, including neurons. Here, we describe a role for Mef2 in the Drosophila pacemaker neurons that regulate circadian behavioral rhythms. We found that Mef2 is normally produced in all adult clock neurons and that Mef2 overexpression in clock neurons ...

HDAC4 (histone deacetylase 4) belongs to class IIa of histone deacetylases, which groups important regulators of gene expression, controlling pleiotropic cellular functions. Here we show that, in addition to the well-defined nuclear/cytoplasmic shuttling, HDAC4 activity is modulated by the ubiquitin-proteasome system. Serum starvation elicits the poly-ubiquitination and degradation of HDAC4 in ...

Histone deacetylases mediate critical cellular functions but relatively little is known about mechanisms controlling their expression, including expression of HDAC4, a Class II HDAC implicated in the modulation of cellular differentiation and viability. Endogenous HDAC4 mRNA, protein levels and promoter activity were all readily repressed by mithramycin, suggesting regulation by GC-rich DNA seq...

إ ةيرهجملا جماربلا لمشي اذهو ،ةيرورملا ةآرحلا ةاآاحم جمارب روطت يف مهاس ةيتامولعملا ايجولونكتلا يف ريبكلا مدقتلا ن ) Microscopic ( ، نلا ىلع بلطلا ةاآاحم اًضيأ لمشي نايحلأا ضعب يفو ، تاعطاقتو قرط نم اهيف امب لقنلا ةموظنم ةاآاحمب حمسيل يللآا بساحلا تاقيبطت قاطنو لق . ةيرهجملا ةيرورملا ةآرحلا ةاآاحم جمارب نيب نراقتو عجارت ةقرولا هذهو ) Microscopic ( ةيلومشلاو ) Macroscopic ( فلاتخلاا هجوأ ىلع ةزآر...

Activation of the inflammatory response is accompanied by a metabolic shift to aerobic glycolysis. Here we identify histone deacetylase 4 (HDAC4) as a new component of the immunometabolic program. We show that HDAC4 is required for efficient inflammatory cytokine production activated by lipopolysaccharide (LPS). Surprisingly, prolonged LPS treatment leads to HDAC4 degradation. LPS-induced HDAC4...

BACKGROUND Osteoarthritis (OA) is the most common degenerative joint disorder, and a major cause of pain and disability among the elderly. Histone deacetylase 4 (HDAC4) has been shown to be a key regulator of chondrocyte hypertrophy during skeletogenesis. The aims of present study were to investigate the expression of HDAC4 in normal and OA cartilage and its potential roles during OA pathogenes...

Gastric cancer (GC) is one of the leading causes of cancer death in the world. The role of histone deacetylase 4 (HDAC4) in specific cell and tissue types has been identified. However, its biological roles in the development of gastric cancer remain largely unexplored. Quantitative real time PCR (qRT-PCR) and western blot were used to analyze the expression of HDAC4 in the clinical samples. siR...

Myocyte enhancer factor-2 (MEF2) transcription factors are activated by p38 mitogen-activated protein kinase during neuronal and myogenic differentiation. Recent work has shown that stimulation of this pathway is antiapoptotic during development but proapoptotic in mature neurons exposed to excitotoxic or other stress. We now report that excitotoxic (N-methyl-D-aspartate) insults to mature cere...