SERPINB13 is a novel RUNX1 target gene

Biochem Biophys Res Commun. 2011 Jul 22;411(1):115-20. doi: 10.1016/j.bbrc.2011.06.107. Epub 2011 Jun 23.

Abstract

RUNX1 is a critical transcription factor during embryogenesis and neoplastic disease. To identify novel transcriptional targets of RUNX1 in the context of chromatin, we performed genome wide location analysis (ChIP-on-chip). Here we report that SERPINB13, a gene downregulated in head and neck cancers, is a novel RUNX1transcriptional target. RUNX1 binds the SERPINB13 promoter in chromatin to repress its transcription. Mutation of either RUNX1 binding site in the SERPINB13 promoter increased the activity of the promoter. Finally, overexpression of RUNX1 and concomitant decrease in SERPINB13 expression led to increased activity of cathepsin K, an enzyme inhibited by SERPINB13. These data demonstrate that RUNX1 is an important regulator of SERPINB13 and cathepsin K activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cathepsin K / biosynthesis
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Core Binding Factor Alpha 2 Subunit / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic
  • Serpins / genetics*
  • Up-Regulation

Substances

  • Core Binding Factor Alpha 2 Subunit
  • RUNX1 protein, human
  • SERPINB13 protein, human
  • Serpins
  • Cathepsin K