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Publication : Cloning and characterization of a novel mouse AP-2 transcription factor, AP-2delta, with unique DNA binding and transactivation properties.

First Author  Zhao F Year  2001
Journal  J Biol Chem Volume  276
Issue  44 Pages  40755-60
PubMed ID  11522791 Mgi Jnum  J:72398
Mgi Id  MGI:2152628 Doi  10.1074/jbc.M106284200
Citation  Zhao F, et al. (2001) Cloning and characterization of a novel mouse ap-2 transcription factor, ap-2delta, with unique DNA binding and transactivation properties. J Biol Chem 276(44):40755-60
abstractText  AP-2 transcription factors are sequence-specific DNA-binding proteins expressed in neural crest and other tissues during mammalian development. Three mammalian genes, AP-2alpha, AP-2beta, and AP-2gamma, have been reported previously. A partial predicted AP-2 gene was identified in tandem with AP-2beta on human chromosome 6p12-p21.1. The orthologous mouse gene, which we named Ap-2delta, was identified from a fetal mouse head cDNA library. Northern analysis revealed two transcripts in embryonic and newborn mouse brain, with markedly higher steady-state levels in the former. The predicted Ap-2delta protein comprised 452 amino acids and was highly similar to other AP-2 proteins across the DNA-binding and dimerization domains. Ap-2delta formed homodimers and heterodimers in vitro, bound an optimized AP-2 consensus DNA sequence, and transactivated gene expression in eukaryotic cells. Ap-2delta dimers bound poorly to an AP-2 binding sequence from the human metallothionein IIa promoter in vitro, revealing a sequence specificity not previously observed among other AP-2 proteins. The PY motif and critical residues in the transactivation domain, which are highly conserved in the AP-2 family and believed necessary for transactivation, were divergent in Ap-2delta. The unique protein sequence and functional features of Ap-2delta suggest mechanisms, besides tissue-specific AP-2 gene expression, for specific control of target gene activation.
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