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 role of two genes, mlcR and ariB, was investigated by gene disruption experiments. The mlcR gene in the ML-236B biosynthetic gene cluster of Penicillium citrinum encodes a putative 50.2-kDa protein with a Zn (II) 2Cys6 DNA-binding domain, and has similarity to most of the GAL4-type regulatory proteins. The mlcR disruptant did not produce ML-236B or its intermediates, suggesting that mlcR is involved in ML-236B biosynthesis. Transcriptional analysis of the mlcR disruptant by Northern hybridization and RT-PCR indicated that MlcR activates the transcription of mlcA, B, C,D, F, G and H in a pathway-specific manner. On the other hand, MlcR did not affect the transcription of mlcE and the genes outside the ML-236B cluster. The ariB gene, next to mlcR, encodes another GAL4-type protein. Transcriptional analysis of the ariB disruptant indicated that it is a transcriptional activator of the genes outside the ML-236B cluster, and is not related to ML-236B biosynthesis.
 ...
PMID:Targeted disruption of the genes, mlcR and ariB, which encode GAL4-type proteins in Penicillium citrinum. 1698 2

MlcR is a pathway-specific transcriptional activator of the ML-236B biosynthetic genes in Penicillium citrinum. The MlcR-binding sequences were identified by an in vitro gel-shift assay and an in vivo reporter assay for the region between mlcA and mlcC as a model. The gel-shift assay showed that recombinant MlcR bound to the DNA sequence 5'-ACGGCGTTATTCGG-3' and most of the bases in this motif were required for the interaction between MlcR and DNA. In the reporter assay using beta-glucuronidase (GUS), substitution of the bases in this binding sequence resulted in the drastic reduction of GUS activities. These data clearly indicate that this MlcR-binding sequence is essential for the transcriptional activation of mlcA and mlcC in P. citrinum. Similar motifs were found in other loci of the ML-236B biosynthetic gene cluster and the consensus-binding motif for MlcR was predicted to be a direct repeat, 5'-WCGG-N(6)-TCGG-3'.
 ...
PMID:Identification of the specific sequence recognized by Penicillium citrinum MlcR, a GAL4-type transcriptional activator of ML-236B (compactin) biosynthetic genes. 1866 69

All of the binding sequences for MlcR, a transcriptional activator of ML-236B (compactin) biosynthetic genes in Penicillium citrinum, were identified by an in vitro gel-shift assay. All the identified sequences contain an asymmetric direct repeat comprised of conserved tetrad bases (A/T)CGG with a spacer sequence of high similarity; in particular, G at position 2 and T at position 3 in the spacer are well conserved. The first (A/T)CGG repeat was essential for MlcR-binding and MlcR could bind to this monomeric site, probably as a monomer. This binding feature might enable MlcR to tolerate the variation of the spacer length and compositions in vitro. From these data, we propose that the consensus binding motif for MlcR is an asymmetric direct repeat, 5'-(A/T)CGG-NGTN(3-6)-TCGG-3'.
 ...
PMID:MlcR, a zinc cluster activator protein, is able to bind to a single (A/T)CGG site of cognate asymmetric motifs in the ML-236B (compactin) biosynthetic gene cluster. 1926 18