Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q02556 (DNA-binding domain)
 6,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The A-Myb and c-Myb transcription factors share a highly conserved DNA-binding domain and activate the same promoters in reporter gene assays. However, the two proteins have distinct biological activities, and expressing them individually in human cells leads to the activation of distinct sets of endogenous genes, suggesting that each protein has a unique transcriptional specificity. Here, the structural and functional features of the Myb proteins were compared, using assays of endogenous gene expression to measure changes in specificity. When the Myb proteins were tested in different cell types, they activated unique and nearly nonoverlapping sets of genes in each cellular context. Deletion and domain swap experiments identified small, discreet positive and negative elements in A-Myb and c-Myb that were required for the regulation of specific genes, such as DHRS2, DSIPI, and mim-1. The results suggest that individual functional elements in the transcriptional activation domains are responsible for activating specific cellular genes in a context-specific manner. The results also have important implications for interpreting results from reporter gene assays, which fail to detect the differences in activity identified through endogenous gene assays, and fusion protein constructs that alter the transcriptional activation domains and the activities of the Myb proteins.
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PMID:Positive and negative determinants of target gene specificity in myb transcription factors. 1510 23

Estrogen has numerous beneficial physiological actions; however, by acting as a mitogen, it plays a significant role in the induction and maintenance of breast cancer. Although the positive effects of estrogen on gene expression are well described, negative gene regulation is not. Using microarray analysis, we identified 27 genes that were up-regulated and 20 that were down-regulated by estrogen in MCF-7 human breast cancer cells. One gene encoding GILZ (glucocorticoid-induced leucine zipper protein), a putative apoptosis-regulating transcription factor, is rapidly down-regulated by estrogen in these cells. Estrogen antagonists block the down-regulation. The region of the GILZ promoter between nucleotides -104 and -69 mediates both basal activity and estrogen-dependent down-regulation in MCF-7 cells. This region contains a functional Oct-1 binding site and a cyclic AMP response element binding protein (CREB) binding site. The same DNA region mediates up-regulation by estrogen in HeLa and HEK293 cells, indicating that cell-specific factors are involved in estrogen regulation of this gene. The estrogen receptor (ER) is present in GILZ promoter protein complexes, but it does not bind directly to the promoter itself, as the DNA-binding domain of the estrogen receptor is not required for down-regulation. Elimination of the CREB binding site blocks both basal activity and estrogen regulation. Our results suggest that ER action at the CRE may mediate estrogen-dependent, cell-specific regulation of this gene.
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PMID:Cell type-specific bidirectional regulation of the glucocorticoid-induced leucine zipper (GILZ) gene by estrogen. 1533