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Figure 8


Fig. 8. MEF2 functions in the endothelium. During embryogenesis, MEF2C expression in the endothelium is dependent on ETS factors, which bind an endothelial cell-specific enhancer. MEF2 activity is also modulated in the endothelium by survival factors, which act through the MAP kinase pathway [MEKK2/3 (also known as MAP3K2/3); MEK5 (also known as MAP2K5)], culminating on ERK5 (MAPK7), which associates with MEF2 directly to enhance transcriptional activity. MEF2 activates transcription of the Mmp10 gene, which encodes a matrix metalloproteinase that degrades endothelial cell junctions. HDAC7, which is expressed specifically in the developing endothelium, represses Mmp10 expression via MEF2. In the absence of HDAC7, MMP10 is upregulated and its inhibitor, TIMP1, is downregulated, leading to a loss in vascular integrity.





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