High impact information on MEF2D

• HDAC7 inhibits the expression of Nur77, an orphan receptor involved in apoptosis and negative selection, via the transcription factor MEF2D [1].
• It has been shown that nuclear factor of activated T cells (NFAT) interacts with MEF2D and enhances its transcriptional activity, offering a plausible mechanism of activation of MEF2D by calcineurin [2].
• The MEF2 domain binds transcription factors MEF2A and MEF2D in vivo [3].
• In contrast, HDAC3 efficiently deacetylated MEF2D in vitro and in vivo [4].
• We report here that treatment of HEK293 cells with trichostatin A or nicotinamide upregulated MEF2D acetylation, suggesting that different deacetylases catalyze the deacetylation [4].

Biological context of MEF2D

• We recently showed that human MEF2D (myocyte enhancer factor 2D) is sumoylated on Lys-439 [5].
• In particular, MEF2D transcripts showed prominent changes by alternative splicing in the perinatal period [6].
• The results from transient transfection and co-precipitation experiments suggest that 14-3-3tau activates MEF2D by competitively inhibiting HDAC4 from binding to MEF2D and thereby affects muscle cell differentiation [7].
• These findings provide compelling evidence that MEF2D is an integral link in the regulatory network for muscle gene expression [8].
• MEF2D has been identified as a candidate oncogene in murine retroviral insertional mutagenesis studies [9].

Anatomical context of MEF2D

• By immunofluorescence, we detected abundant nuclear localized MEF2A and MEF2D protein expression in HeLa cells and C2C12 muscle cells [10].
• These results show that MEF2D is required in the differentiation process along the monocyte/macrophage lineage,[11]
• To examine the role of MEF2, we expressed a dominant-negative form of MEF2D, without its transactivation domain, in HL60 cells [11].
• Transfection of MEF2D into NIH 3T3 cells reconstituted serum induction, demonstrating that MEF2D is required for the serum response [12].
• The MEF2A and MEF2D isoforms are differentially regulated in muscle and adipose tissue during states of insulin deficiency [13].

Physical interactions of MEF2D

• Furthermore, immunodepletion of the MEF2A-MEF2D complex from control extracts abolished binding to the MEF2 element [14].

Regulatory relationships of MEF2D

• These data strongly suggest that the MEF2A-MEF2D heterodimer is selectively decreased in insulin-deficient diabetes and is responsible for hormonally regulated expression of the GLUT4 gene [14].
• Transient transfection experiments showed that co-expression of MEF2D and Sp1 synergistically activated the CD14 promoter [15].
• Like its relatives, cloned hMEF2D is capable of activating transcription via sequence-specific binding to the MEF2 site, recapitulating endogenous tissue-specific MEF2 activity [8].
• MEF2D has been known to regulate Nur77 expression in a calcium- dependent manner [16].

Other interactions of MEF2D

• These changes seemed to be correlated with the alternative splicing changes of MEF2 genes, especially MEF2D [6].
• The sites phosphorylated by activated BMK1 were mapped to Ser-355, Thr-312, and Thr-319 of MEF2A and Ser-179 of MEF2D both in vitro and in vivo [17].
• Transient co-expression of p300, MEF2D, NFATp and constitutively active calcineurin is sufficient to recapitulate TCR signaling for the selective induction of the endogenous Nur77 gene [2].
• We also show that DAZAP1/MEF2D is a sequence-specific RNA-binding protein [9].
• Synergistic interaction of MEF2D and Sp1 in activation of the CD14 promoter [15].

Analytical, diagnostic and therapeutic context of MEF2D

• In addition to the SRT-NCC27/CLIC1, SRT10 could detect N-terminal-tagged MEF2D and C-terminal-tagged CD4 by immunocytochemistry [18].

References