Characterization of the promoter of the human KAL gene, responsible for the X-chromosome-linked Kallmann syndrome

Gene. 1995 Oct 27;164(2):235-42. doi: 10.1016/0378-1119(95)00481-k.

Abstract

We report on the first characterization of the human KAL promoter (pKAL), based on the analysis of a 2-kb fragment of the 5' flanking region. As determined by primer extension, transcription of the human KAL gene is initiated at two different sites in the quail embryonic neuroretina QNR/D cell line. The promoter region is G+C rich and contains a CCAAT box, two binding sites for the SP1 transcription factor and two AP2-binding sites, but no TATA box. It also shares a motif with several neural-specific genes. The ability of four deletion mutants to drive transcription of the heterologous chloramphenicol acetyltransferase (CAT)-encoding gene was determined in transfection experiments. The mutant containing the KAL sequence from nt +2 to -435 demonstrated a tissue-specific, although weak, transcriptional activity only in the quail embryonic neuroretina K2 and QNR/D cell lines. Longer constructs did not confer any activity. Therefore, we suggest that this 437-bp segment of pKAL constitutes a neural-specific promoter which could be negatively controlled by upstream sequences.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Chloramphenicol O-Acetyltransferase / biosynthesis
  • DNA Primers
  • Extracellular Matrix Proteins*
  • Hominidae / genetics*
  • Humans
  • Kallmann Syndrome / genetics*
  • Molecular Sequence Data
  • Mutagenesis
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics*
  • Nuclear Proteins / isolation & purification
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic*
  • Recombinant Proteins / biosynthesis
  • Restriction Mapping
  • Sequence Deletion
  • Sequence Homology, Nucleic Acid
  • TATA Box
  • Transcription, Genetic
  • Transfection
  • X Chromosome*

Substances

  • ANOS1 protein, human
  • DNA Primers
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Recombinant Proteins
  • Chloramphenicol O-Acetyltransferase

Associated data

  • GENBANK/X82034