A bipartite activation domain is responsible for the activity of transcription factor HNF1/LFB1 in cells of hepatic and nonhepatic origin

C. Toniatti, P. Monaci, A. Nicosia, R. Cortese, G. Ciliberto

Research output: Contribution to journalArticle

Abstract

HNF1/LFB1 is a transcription factor that controls the expression of several liver-specific genes. Previous in vitro experiments allowed us to identify two different regions in the carboxy-terminal portion of the protein responsible for most of the transcription activation potential: the first, ADI, between amino acids 546 and 628 and the second, ADII, between amino acids 281 and 318. To characterize the molecular anatomy of HNF1/LFB1 better, we have analyzed its trans-activating properties in vivo. Several HNF1/LFB1 deletion mutants were tested for their ability to induce transcription from HNF1/LFB1-dependent synthetic promoters in cells of hepatic and nonhepatic origin. These last recipient cells provide an HNF1/LFB1-deficient environment that is useful for a precise quantification of the recombinant protein. Our results confirm the importance of ADI and indicate that no activating property can be assigned to ADII in vivo. Moreover, a novel glutamine/proline-rich activation domain (ADIII) has been identified between amino acids 440 and 506. These findings are confirmed by domain-swapping experiments, carried out with the heterologous GAL4 DNA-binding domain, which also show that the activity of each individual activation domain is influenced by combining adjacent HNF1/LFB1 sequences. The data presented indicate that HNF1/LFB1 transcription activating potential relies on a complex structure and also provide important clues to understanding the different functions exerted by transcription factors of this family.

Original languageEnglish
Pages (from-to)199-208
Number of pages10
JournalDNA and Cell Biology
Volume12
Issue number3
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

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