Brawn for Brains: The Role of MEF2 Proteins in the Developing Nervous System

Shalizi, Aryaman; Bonni, Azad

doi:10.1016/s0070-2153(05)69009-6

Cited by 78 publications

(85 citation statements)

References 156 publications

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“…We propose that this provides for both positive and negative autoregulation of MEF2A transcription by MEF2A proteins, contributing to a wide dynamic range of MEF2A expression. Because all MEF2 factors share a common N-terminal MADS/ MEF2 region with dimerization and sequence-specific DNA binding activities (5,6), protein products of the other MEF2 isotype genes, i.e. MEF2B, MEF2C, MEF2D, are also predicted to regulate MEF2A transcription.…”

Section: Discussionmentioning

confidence: 99%

“…MEF2 (myocyte enhancer factor 2) proteins are a subset of the minichromosome maintenance/agamous/deficiens/serum-response factor (MADS) 5 box transcription factor superfamily (1). MEF2A was the first MEF2 to be identified (2,3), and four splicing variants are encoded by the MEF2A gene of all vertebrates (4).…”

mentioning

confidence: 99%

“…MEF2A was the first MEF2 to be identified (2,3), and four splicing variants are encoded by the MEF2A gene of all vertebrates (4). 6 Three additional mammalian MEF2 isotypes, MEF2B, MEF2C, and MEF2D, were subsequently described (5,6). Other metazoans, from Porifera to Chordata, also have MEF2 genes.…”

mentioning

confidence: 99%

“…Other metazoans, from Porifera to Chordata, also have MEF2 genes. All MEF2 proteins have an N-terminal MADS box and an adjacent MEF2-specific signature domain that function together to specify MEF2 dimerization and sequence-specific dimer binding to CTA(T/A) 4 TAR (or YTA(T/A) 4 TAG) sequences in the regulatory regions of target genes (1,5,6).…”

mentioning

confidence: 99%

“…In contrast to extensive work on MEF2/MEF2 regulation at levels of modifications in response to signaling (5, 7, 18, 26 -28) and transcription factor and co-regulator interactions (5,6,29), and some studies of translational (30) and pre-mRNA splicing control (4,31), examination of MEF2 gene transcription has been limited to studies of Drosophila Mef2 (32,33) and murine mef2c (34 -36). As an initial step in the analysis of MEF2A transcriptional regulation, we report here the mapping and partial characterization of the highly conserved 5Ј-regulatory region of the mammalian MEF2A gene.…”

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confidence: 99%

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Myocyte Enhancer Factor 2A Is Transcriptionally Autoregulated

Ramachandran

et al. 2008

Journal of Biological Chemistry

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MEF2 (myocyte enhancer factor 2) proteins are a small family of transcription factors that play pivotal roles in striated muscle differentiation, development, and metabolism, in neuron survival and synaptic formation, and in lymphocyte selection and activation. Products of the four mammalian MEF2 genes, MEF2A, MEF2B, MEF2C, and MEF2D, are expressed with overlapping but distinct temporospatial patterns. Toward analysis of MEF2A functions and the determinants of its regulated expression, we have mapped and begun studies of the transcriptional control regions of this gene. Heterogeneous 5 -untranslated regions of MEF2A mRNAs result from use of alternative promoters and splicing patterns. The two closely approximated TATA-less promoters are ϳ65 kb upstream of the exon containing the sole initiation codon. Ribonuclease protection and primer extension assays show that each promoter is active in various adult tissues. A canonical MEF2 site overlies the major promoter 1 transcription start site. This element specifically binds MEF2 factors, including endogenous nuclear MEF2A according to chromatin immunoprecipitation studies, and is critical to MEF2A transcription in myocytes. The site exerts reciprocal control of the alternative promoters, silencing promoter 1 and activating promoter 2 under some conditions. Erk5 and p38 MAPK signaling stimulate MEF2A expression by activating both promoters from the MEF2 element. MEF2A transcription is therefore subject to positive or negative regulation by its protein products, depending on signaling activities that influence MEF2 factor trans-activity. The sole MEF2 gene of the cephalochordate amphioxus has a similar regulatory region structure, suggesting that this mode of autoregulatory control is conserved among higher metazoan MEF2 genes.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Myocyte Enhancer Factor 2A Is Transcriptionally Autoregulated

Ramachandran

et al. 2008

Journal of Biological Chemistry

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Cabin1 expression suggests roles in neuronal development

Hammond

Udvadia

2010

Developmental Dynamics

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*Nervous system assembly and function depends on precise regulation of developmental gene expression. Cabin1, an essential gene in developing mice, is enriched in regions of the developing zebrafish central nervous system (CNS). Cabin1 is a repressor of MEF2-(myocyte enhancer factor 2) and calcineurin-mediated transcription in the immune system, but its function in the CNS during development is unknown. We identified Cabin1 from a library of genes enriched in developing neurons and determined the temporal and spatial expression of Cabin1 mRNA during CNS development. We found Cabin1 mRNA expression in the developing brain at times correlated with later aspects of neuronal differentiation. In some regions of the CNS Cabin1 expression overlaps with regions that also express proteins known to interact with Cabin1: MEF2 and/or calcineurin. We suggest that Cabin1 could act as a regulator of MEF2 and calcineurin activity in the developing nervous system, given their roles in neuronal differentiation and synaptic refinement. Developmental Dynamics 239:2443-2451,

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Neuroprotective Activity of pDING in Response to HIV‐1 Tat

Darbinian

Khalili

Amini

2013

Journal Cellular Physiology

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Although neurons are not productively infected with HIV-1, neuronal injury and death are frequently seen in the brains of AIDS patients with neurological and neurocognitive disorders. Evidently, viral proteins including Tat and cellular inflammatory factors released by activated and/or infected microglia, macrophages, and astrocytes contribute to neuronal cell death. Several studies have demonstrated that HIV-1 associated neuronal cell injury is mediated by dysregulation of signaling pathways that are controlled, in part, by a class of serine/threonine kinases. In this study we demonstrate that pDING, a novel plant-derived phosphate binding protein has the capacity to reduce the severity of injury and death caused by HIV-1 and its neurotoxic Tat protein. We demonstrate that pDING, also called p27SJ/p38SJ, protects cells from the loss of neuronal processes induced by Tat and promotes neuronal outgrowth after Tat-mediated injury. Further, expression of pDING prevents Tat-induced oxidative stress and mitochondrial permeability. With its profound phosphatase activity, pDING controls the activity of several kinases including MAPK, Cdk5 and their downstream target protein, MEF2, which is implicated in neuronal cell protection. Our results show that expression of pDING in neuronal cells diminishes the level of hyperphosphorylated forms of Cdk5 and MEF2 caused by Tat and the other neurotoxic agents that are secreted by the HIV-1 infected cells. These observations suggest that pDING, through its phosphatase activity, has the ability to manipulate the state of phosphorylation and activity of several factors involved in neuronal cell health in response to HIV-1.

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Brawn for Brains: The Role of MEF2 Proteins in the Developing Nervous System

Cited by 78 publications

References 156 publications

Myocyte Enhancer Factor 2A Is Transcriptionally Autoregulated

Myocyte Enhancer Factor 2A Is Transcriptionally Autoregulated

Cabin1 expression suggests roles in neuronal development

Neuroprotective Activity of pDING in Response to HIV‐1 Tat

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