2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 56(2022) N 1 p. 90-96; DOI 10.1134/S0026893322010095 Full Text

A.N. Uvarova1,2, A.S. Ustiugova1, N.A. Mitkin1, A.M. Schwartz1, K.V. Korneev1, D.V. Kuprash1,2*

The Minor T Allele of the Single Nucleotide Polymorphism rs 13360222 Decreases the Activity of the HAVCR2 Gene Enhancer in a Cell Model of Human Macrophages

1Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2Faculty of Biology, Moscow State University, Moscow, 119234 Russia

Received - 2021-08-16; Revised - 2021-09-08; Accepted - 2021-09-08

The TIM-3 receptor, encoded by the Hepatitis A Virus Cellular Receptor 2 (HAVCR2) gene, is an immune checkpoint and plays an important role in preventing the development of autoimmune reactions. This receptor is expressed on the surface of various immunocytes and its functions in myeloid cells remain poorly understood, compared to the role of T cell specific TIM-3 that is actively studied in the context of the search for promising therapeutic targets in cancer immunotherapy. During this study, we performed deletion analysis of the promoter region of the HAVCR2 gene, as well as functional characterization of its enhancer, and studied the effect of a number of single nucleotide polymorphisms (SNPs) on the activity of these regulatory elements in the relevant model of human macrophage-like cells-U937 activated monocytes. We have shown that the SNPs rs10515746(A) and rs4704853(A) located in the HAVCR2 gene promoter and associated with the development of a number of pathologies, do not affect the activity of the promoter in activated monocytes. However, a minor T variant of SNP rs13360222 located in the enhancer in the third intron of the gene, significantly reduces the ability of the enhancer to activate the HAVCR2 promoter, presumably due to weakening of the binding of nuclear receptor ESR2 to the respective region.

HAVCR2, TIM-3, single nucleotide polymorphisms, transcription regulation, promoter, enhancer