Back to Search
Start Over
Surface plasmon resonance based analysis of the binding of LYAR protein to the rs368698783 (G>A) polymorphic Aγ-globin gene sequences mutated in β-thalassemia.
- Source :
- Analytical & Bioanalytical Chemistry; Nov2019, Vol. 411 Issue 29, p7699-7707, 9p
- Publication Year :
- 2019
-
Abstract
- Recent studies have identified and characterized a novel putative transcriptional repressor site in a 5′ untranslated region of the Aγ-globin gene that interacts with the Ly-1 antibody reactive clone (LYAR) protein. LYAR binds the 5'-GGTTAT-3' site of the Aγ-globin gene, and this molecular interaction causes repression of gene transcription. In β-thalassemia patients, a polymorphism has been demonstrated (the rs368698783 G>A polymorphism) within the 5′-GGTTAT-3′ LYAR-binding site of the Aγ-globin gene. The major results gathered from surface plasmon resonance based biospecific interaction analysis (SPR-BIA) studies (using crude nuclear extracts, LYAR-enriched lysates, and recombinant LYAR) support the concept that the rs368698783 G>A polymorphism of the Aγ-globin gene attenuates the efficiency of LYAR binding to the LYAR-binding site. This conclusion was fully confirmed by a molecular docking analysis. This might lead to a very important difference in erythroid cells from β-thalassemia patients in respect to basal and induced levels of production of fetal hemoglobin. The novelty of the reported SPR-BIA method is that it allows the characterization and validation of the altered binding of a key nuclear factor (LYAR) to mutated LYAR-binding sites. These results, in addition to theoretical implications, should be considered of interest in applied pharmacology studies as a basis for the screening of drugs able to inhibit LYAR–DNA interactions. This might lead to the identification of molecules facilitating induced increase of γ-globin gene expression and fetal hemoglobin production in erythroid cells, which is associated with possible reduction of the clinical severity of the β-thalassemia phenotype. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16182642
- Volume :
- 411
- Issue :
- 29
- Database :
- Complementary Index
- Journal :
- Analytical & Bioanalytical Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 139883163
- Full Text :
- https://doi.org/10.1007/s00216-019-01987-9