LFB1/HNF1 acts as a repressor of its own transcription.
AUTOR(ES)
Piaggio, G
RESUMO
LFB1/HNF1 is a hepatocyte-enriched trans-activator involved in the regulation of many liver-specific genes. We report the cloning and characterization of a rat genomic DNA fragment containing about 3.5 kb of the LFB1/HNF1 gene 5'-flanking region. This DNA segment is capable of directing the liver-specific expression of a reporter gene in transfection assays. More interestingly, the basal activity of the LFB1/HNF1 promoter in cultured hepatoma cell lines is down-regulated by exogenously added LFB1/HNF1 protein itself. The ability to repress transcription starting from its own promoter requires the integrity of the N-terminal LFB1/HNF1 DNA-binding domain. Contrary to the expectations, in vitro binding experiments failed to demonstrate any specific and functional interaction of purified LFB1/HNF1 with the -3.5 kb promoter sequence. In addition to the DNA-binding domain, a 60 aa region contained in the C-terminus of the protein and distinct from the previously characterized activation domains, is also required for the repressing function.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=331944Documentos Relacionados
- The X-ray structure of an atypical homeodomain present in the rat liver transcription factor LFB1/HNF1 and implications for DNA binding.
- The three-dimensional NMR-solution structure of the polypeptide fragment 195-286 of the LFB1/HNF1 transcription factor from rat liver comprises a nonclassical homeodomain.
- A POU-A related region dictates DNA binding specificity of LFB1/HNF1 by orienting the two XL-homeodomains in the dimer.
- Yeast SKO1 gene encodes a bZIP protein that binds to the CRE motif and acts as a repressor of transcription.
- Lambda repressor turns off transcription of its own gene.