Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The beta 3 tubulin gene (beta Tub60D) is a structural gene expressed during mesoderm development from the extended germ band stage onward. Expression within the individual mesodermal derivatives is guided by different control elements. The upstream regions allow expression in the dorsal vessel and the somatic mesoderm while enhancers localized in the first intron guide expression in the visceral mesoderm. Deletion analysis carried out in transgenic flies revealed independent regulatory elements for the dorsal vessel and the somatic mesoderm. For expression in the somatic mesoderm, a 279-bp region is absolutely essential. This region contains a binding site for the Drosophila myocyte-specific enhancer binding factor 2 (D-MEF2), a MADS-box transcription factor known to be essential for mesoderm development. Deletion or mutation of this D-MEF2 binding site strongly reduces transcription. This pattern is consistent with the strongly reduced expression of beta 3 tubulin in D-mef2 mutant embryos. This analysis furthermore reveals that the D-MEF2 binding site acts in concert with nearby cis regulatory elements. These data show that the upstream control region of the beta 3 tubulin gene is an early target of the D-MEF2 transcriptional activator.
 ...
PMID:Independent regulatory elements in the upstream region of the Drosophila beta 3 tubulin gene (beta Tub60D) guide expression in the dorsal vessel and the somatic muscles. 967 98

Members of the myocyte enhancer factor 2 (MEF2) family of transcription factors contain highly conserved sequences within their MADS box and MEF2 domain. These motifs are required for DNA binding and dimerization properties, as well as for MEF2 association with various transcriptional activator or repressor proteins. The D-mef2 gene encodes the MEF2 protein of Drosophila and genetic studies have shown that normal D-MEF2 function is needed for muscle cell differentiation during embryogenesis and indirect flight muscle formation during pupal development. We have characterized three additional lethal alleles of D-mef2 and identified the specific mutation in each that alters a conserved amino acid present within the MADS box of all known MEF2 proteins. Mutation of these invariant residues results in the inability of mutant D-MEF2 proteins to bind DNA in vitro, muscle defects within the embryo, and adverse effects on the structure of indirect flight muscles within the adult. Since the crystal structure of a MEF2 core protein bound to DNA has been previously solved, our results correlate the mutation of specific MADS box amino acids utilized for target DNA recognition with severe myogenic phenotypes manifested during Drosophila development.
 ...
PMID:Mutations within the conserved MADS box of the D-MEF2 muscle differentiation factor result in a loss of DNA binding ability and lethality in Drosophila. 1236 81