Human leukocyte elastase gene expression is regulated by PU.1 in conjunction with closely associated cytidine-rich and Myb binding sites

  • Sturrock A
  • Franklin K
  • Norman K
 et al. 
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Abstract

Leukocyte elastase (LE) degrades connective tissue, is involved in the inflammatory process and implicated in cyclic and congenital neutropenia. The human LE gene is within a serine proteinase locus on chromosome 19 pter13.3. Our observations demonstrate that LE gene expression is regulated by PU.1, a cytidine-rich and a Myb binding site. The LE promoter has two cytidine-rich sites at -158 and -185. The -158 is the active site and it is closest to the PU.1 site. Proximity is essential to activity since separation of the -158 and PU.1 sites by a 20-base pair oligonucleotide reduced promoter activity by 50%. This suggests physical interaction between the transcription proteins binding to the PU.1 and -158 sites. The nuclear protein that binds the -158 site is present in B and T lymphocytes and an erythroleukemia cell line in addition to being abundant in the promyelocytic stage of neutrophil maturation when the LE gene is expressed. The protein binding to the -158 site is absent or expressed at low levels in non-hematopoietic cell lines. We have identified the transcription factors essential for human LE gene expression. Comparison with the mouse LE gene shows similarities and differences. © 2003 Published by Elsevier B.V.

Author-supplied keywords

  • Cytidine-rich site
  • Gene transcription
  • Leukocyte elastase
  • PU.1
  • Serine proteinase

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Authors

  • Anne Sturrock

  • Kerry F. Franklin

  • Kimberly Norman

  • John R. Hoidal

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