Identification of strong intron enhancer in the heparanase gene: effect of functional rs4693608 variant on HPSE enhancer activity in hematological and solid malignancies.

ABSTRACT: Heparanase is an endo-β-glucuronidase that specifically cleaves the saccharide chains of heparan sulfate (HS) proteoglycans and releases HS-bound cytokines, chemokines, and bioactive growth-promoting factors. Heparanase plays an important role in the nucleus as part of an active chromatin complex. Our previous studies revealed that rs4693608 correlates with heparanase levels and increased risk of acute and extensive chronic graft vs. host disease (GVHD). Discrepancy between recipient and donor in this SNP significantly affected the risk of acute GVHD. In the present study, we analyzed the HPSE gene region, including rs4693608, and demonstrated that this region exhibits SNPs-dependent enhancer activity. Analysis of nuclear proteins from normal leukocytes revealed their binding to DNA probe

SUBMITTER: Ostrovsky O 

PROVIDER: S-EPMC6023935 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature