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Enhanced C/EBP binding to G·T mismatches facilitates fixation of CpG mutations in cancer and adult stem 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: 7 июля 2021 г.
- Авторы: Ershova A.S., Eliseeva I.A., Nikonov O.S., Fedorova A.D., Vorontsov I.E., Papatsenko D., Kulakovskiy I.V.
- Журнал: Cell reports
- Том: 35
- Номер: 10
- Год издания: 2021
- Издательство: Cell Press
- Местоположение издательства: United States
- Номер статьи: 109221
- DOI: 10.1016/j.celrep.2021.109221
- Аннотация: Somatic mutations in regulatory sites of human stem cells affect cell identity or cause malignant transformation. By mining the human genome for co-occurrence of mutations and transcription factor binding sites, we show that C/EBP binding sites are strongly enriched with [C > T]G mutations in cancer and adult stem cells, which is of special interest because C/EBPs regulate cell fate and differentiation. In vitro protein-DNA binding assay and structural modeling of the CEBPB-DNA complex show that the G·T mismatch in the core CG dinucleotide strongly enhances affinity of the binding site. We conclude that enhanced binding of C/EBPs shields CpG·TpG mismatches from DNA repair, leading to selective accumulation of [C > T]G mutations and consequent deterioration of the binding sites. This mechanism of targeted mutagenesis highlights the effect of a mutational process on certain regulatory sites and reveals the molecular basis of putative regulatory alterations in stem cells.
- Добавил в систему: Ершова Анна Степановна