Laboratory of Transcriptional Regulation(PAS, Lodz) in cooperation with Biobank Lab (University of Lodz) published new paper about detection of polymorphisms in promoter region of RORγT gene and its functional consequences. Paper is published in Genes (IF=3,242). Enjoy your lecture.


"Functional Analysis of the rs774872314, rs116171003, rs200231898 and rs201107751 Polymorphisms in the Human RORγT Gene Promoter Region"


Marcin Ratajewski1, Marcin Słomka2, Kaja Karaś1, Marta Sobalska-Kwapis2, Małgorzata Korycka-Machała3, Anna Sałkowska1, Jarosław Dziadek3, Dominik Strapagiel2, Jarosław Dastych4.
1Laboratory of Transcriptional Regulation, Institute of Medical Biology, PAS, Lodz, Poland.
2Biobank Lab, Department of Molecular Biophysics, University of Lodz, Lodz, Poland.
3Mycobacterium Genetics and Physiology Unit, Institute of Medical Biology, PAS, Lodz, Poland.
4Laboratory of Cellular Immunology, Institute of Medical Biology, PAS, Lodz, Poland.


RAR-related orphan receptor gamma RORγT, a tissue-specific isoform of the RORC gene, plays a critical role in the development of naive CD4+ cells into fully differentiated Th17 lymphocytes. Th17 lymphocytes are part of the host defense against numerous pathogens and are also involved in the pathogenesis of inflammatory diseases, including autoimmune disorders. In this study, we functionally examined four naturally occurring polymorphisms located within one of the previously identified GC-boxes in the promoter region of the gene. The single nucleotide polymorphisms (SNPs) rs774872314, rs116171003 and rs201107751 negatively influenced the activity of the RORγT promoter in a gene reporter system and eliminated or reduced Sp1 and Sp2 transcription factor binding, as evidenced by the electrophoretic mobility shift assay (EMSA) technique. Furthermore, we investigated the frequency of these SNPs in the Polish population and observed the presence of rs116171003 at a frequency of 3.42%. Thus, our results suggest that polymorphisms within the RORγT promoter occurring at significant rates in populations affect promoter activity. This might have phenotypic effects in immune systems, which is potentially significant for implicating pathogenetic mechanisms under certain pathological conditions, such as autoimmune diseases and/or primary immunodeficiencies (e.g., immunoglobulin E (IgE) syndrome). 
Keywords: RORγT; RORC; Th17; promoter; polymorphism
This work was supported by National Science Centre Grant 2015/18/E/NZ5/00733. Populous collection was supported by the Polish POIG Grant 01.01.02-10-005/08 TESTOPLEK from the European Regional Development Fund.

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