LFB1/HNF1 acts as a repressor of its own transcription

Giulia Piaggio, Licia Tomei, Carlo Toniatti, Raffaele De Francesco, Jutta Gerstner, Riccardo Cortese

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)4284-4290
Number of pages7
JournalNucleic Acids Research
Volume22
Issue number20
Publication statusPublished - Oct 11 1994

ASJC Scopus subject areas

  • Genetics
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Health, Toxicology and Mutagenesis
  • Toxicology
  • Genetics(clinical)

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