INTRODUCTION: MMP‑9‑1562C/T modulates MMP‑9 mRNA expression and consequently influences the course of many human diseases that involve pathology of this metalloproteinase (e.g., stroke, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, cardiovascular diseases). Until now, the precise molecular mechanism of MMP‑9‑1562C/T‑dependent influence on MMP‑9 gene expression has not been discovered. AIM(S): The purpose of this study is to identify transcriptional regulators binding to MMP‑9‑1562C/T and to evaluate their influence on MMP‑9 expression in human neurons. METHOD(S): The studies are carried out in differentiated neurons derived from the SH-SY5Y human neuroblastoma cell line. We showed, by luciferase assay, that transcriptional activity of the T allele is higher than the C allele in human neurons. We also studied interactions of nuclear proteins with MMP‑9‑1562C/T polymorphism by EMSA (Electrophoretic Mobility Shift Assay). We found that nucleoprotein complexes form in an allele‑specific manner in human neurons. Using magnetic beads coated with the human allele C or T, we pulled down nuclear proteins binding specifically to the alleles. Then, we analyzed the identity of these proteins using mass spectrometry. CONCLUSIONS: As a result, we identified numerous transcriptional regulators and co-regulators that may be involved in the allele‑specific modulation of MMP‑9 expression in human neurons.
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