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Minor C allele of the SNP rs7873784 associated with rheumatoid arthritis and type-2 diabetes mellitus binds PU.1 and enhances TLR4 expressionстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Korneev Kirill V., Sviriaeva Ekaterina N., Mitkin Nikita A., Gorbacheva Alisa M., Uvarova Aksinya N., Ustiugova Alina S., Polanovsky Oleg L., Kulakovskiy Ivan V., Afanasyeva Marina A., Schwartz Anton M., Kuprash Dmitry V.
- Журнал: Biochimica et Biophysica Acta - Molecular Basis of Disease
- Год издания: 2019
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- DOI: 10.1016/j.bbadis.2019.165626
- Аннотация: Toll-like receptor 4 (TLR4) is an innate immunity receptor predominantly expressed on myeloid cells and involved in the development of various diseases, many of them with complex genetics. Here we present data on functionality of single nucleotide polymorphism rs7873784 located in the 3′-untranslated region (3′-UTR) of TLR4 gene and associated with various pathologies involving chronic inflammation. We demonstrate that TLR4 3′-UTR strongly enhanced the activity of TLR4 promoter in U937 human monocytic cell line while minor rs7873784(C) allele created a binding site for transcription factor PU.1 (encoded by SPI1 gene), a known regulator of TLR4 expression. Increased binding of PU.1 further augmented the TLR4 transcription while PU.1 knockdown or complete disruption of the PU.1 binding site abrogated the effect. We hypothesize that additional functional PU.1 site may increase TLR4 expression in individuals carrying minor C variant of rs7873784 and modulate the development of certain pathologies, such as rheumatoid arthritis and type-2 diabetes mellitus.
- Добавил в систему: Уварова Аксинья Николаевна