Disease relevance of Adf1

• Purified recombinant Adf-1 expressed in Escherichia coli binds specifically to Adf-1 recognition sites and activates transcription of a synthetic Adh promoter in vitro in a manner indistinguishable from the protein purified from Drosophila [1].
• Establishment of DNase hypersensitivity required the presence of both GAGA and Adf-1 binding sites and was accompanied by a further, synergistic increase in transcription [2].

High impact information on Adf1

• Adf-1 binds at least one of these proximal promoter regions but interaction at this site is not specifically required for transcription [3].
• Studies at the larval neuromuscular junction, however, reveal a role for Adf1 in the modulation of synaptic growth-in contrast to the role established for dCREB2 in the control of synaptic function (Davis et al., 1996) [4].
• The complete amino acid sequence of Adf-1 deduced from the longest cDNA reveals structural similarities to the putative helix-turn-helix DNA binding motif of Myb and Myb-related proteins [1].
• We have cloned the cDNA encoding Adf-1 by generating specific DNA probes deduced from partial amino acid sequence of the protein [1].
• DNA sequence analysis of genomic clones and Northern blot analysis of mRNA suggest that Adf-1 is a single-copy gene encoding a 1.9-kb transcript [1].

Biological context of Adf1

• The presence of putative binding sites for GAGA and Adf1 transcription factors may indicate a cross regulatory mechanism with other chromatin regulators [5].
• During later stages of embryogenesis, Adf-1 appears to be expressed in the nucleus of most somatic cells in the embryo with possibly higher concentrations found in some tissues [1].
• We have carried out a mutational analysis of the Adh distal promoter using both an in vitro transcription assay and a transient transfection assay in Drosophila tissue culture cells, and in both cases find that deletion of sequences required for Adf-1 binding leads to a 3-4-fold drop in transcription [6].
• These distant upstream elements must interact with the promoter elements, the Adf-1-binding site and the TATA box, as they only influenced transcription when at least one of these two positive distal promoter elements was present [7].
• We have performed a comprehensive mapping of the functional domains of Adf-1 to study the role of transactivators in the process of gene activation [8].

Anatomical context of Adf1

• Stonewall is a germ cell nuclear protein; Stonewall has a DNA binding domain that shows similarities to the Myb and Adf-1 transcription factors and has other features that suggest that it is a transcription activating factor [9].

Associations of Adf1 with chemical compounds

• We have purified Adf-1 and demonstrate by a sodium dodecyl sulfate-gel renaturation assay that it is a 34-kDa protein [6].

Physical interactions of Adf1

• Because Adf-1 is capable neither of establishing a DH site nor of promoting efficient transcription by itself in embryos, it is likely that DH site formation depends on a GAGA factor-mediated binding of Adf-1 to chromatin, perhaps facilitated by a locally remodeled downstream promoter region [2].

Other interactions of Adf1

• Dip3 possesses an N-terminal MADF domain and a C-terminal BESS domain, an architecture that is conserved in at least 14 Drosophila proteins, including Adf-1 and Stonewall [10].
• Cloning of Drosophila transcription factor Adf-1 reveals homology to Myb oncoproteins [1].
• Thus, it appears that Adf-1 may play an important role not only in the regulation of Adh expression but also in the transcription of other Drosophila genes as well [6].
• In one particular nucleosome position, the wrapping of the Adf-1 and adjacent GAGA factor binding sitesaround the histone octamer creates a unique local DNA conformation [11].
• Expression of the Drosophila melanogaster ATP synthase alpha subunit gene is regulated by a transcriptional element containing GAF and Adf-1 binding sites [12].

References