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Protective C allele of the single-nucleotide polymorphism rs1335532 is associated with strong binding of Ascl2 transcription factor and elevated CD58 expression in B-cellsстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 28 октября 2018 г.
- Авторы: Mitkin Nikita A., Muratova Alisa M., Korneev Kirill V., Pavshintsev Vsevolod V., Rumyantsev Konstantin A., Vagida Murad S., Uvarova Aksinya N., Afanasyeva Marina A., Schwartz Anton M., Kuprash Dmitry V.
- Журнал: Biochimica et Biophysica Acta - Molecular Basis of Disease
- Том: 1864
- Номер: 10
- Год издания: 2018
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: 3211
- Последняя страница: 3220
- DOI: 10.1016/j.bbadis.2018.07.008
- Аннотация: CD58 is expressed on the surface of antigen-presenting cells, including B-cells, and provides co-stimulation to regulatory T-cells (Treg) through CD2 receptor binding. Tregs appear to be essential suppressors of tissue-specific autoimmune responses. Thereby, CD58 plays protective role in multiple sclerosis (MS) and CD58 was identified among several loci associated with MS susceptibility. Minor (C) variant of the single-nucleotide polymorphism (SNP) rs1335532 is associated with lower MS risk according to genome-wide association studies (GWAS) and its presence correlates with higher CD58 mRNA levels in MS patients. We found that genomic region containing rs1335532 has enhancer properties and can significantly boost the CD58 promoter activity in lymphoblast cells. Using bioinformatics and pull-down assay we found that the protective (C) rs1335532 allele created functional binding site for ASCL2 transcription factor, a target of the Wnt signaling pathway. Both in B-lymphoblastoid cell lines and in primary B-cells, as well as in a monocytic cell line, activation of Wnt signaling resulted in an increased CD58 promoter activity in the presence of the protective but not the risk allele of rs1335532, whereas ASCL2 knockdown abrogated this effect. In summary, our results suggest that ASCL2 mediates the protective function of rs1335532 minor (C) allele in MS.
- Добавил в систему: Горбачева Алиса Михайловна