Human-specific endogenous retroviral insert serves as an enhancer for the schizophrenia-linked gene

Suntsova, M.; Gogvadze, E.; Salozhin, S.; Gaifullin, N.; Eroshkin, F.; Dmitriev, S.; Martynova, N.; Kulikov, K.; Malakhova, G.; Tukhbatova, G.; Bolshakov, A.; Ghilarov, D.; Garazha, A.; Aliper, A.; Cantor, C.; Solokhin, Y.; Roumiantsev, S.; Balaban, P.; Zhavoronkov, A.; Buzdin, A.

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 сентября 2018 г.

Авторы: Suntsova M., Gogvadze EV, Salozhin S., Gaifullin N., Eroshkin F., Dmitriev SE, Martynova N., Kulikov K., Malakhova G., Tukhbatova G., Bolshakov AP, Ghilarov D., Garazha A., Aliper A., Cantor CR, Solokhin Y., Roumiantsev S., Balaban P., Zhavoronkov A., Buzdin A.
Журнал: Proceedings of the National Academy of Sciences of the United States of America
Том: 110
Номер: 48
Год издания: 2013
Издательство: National Academy of Sciences
Местоположение издательства: United States
Первая страница: 19472
Последняя страница: 19477
DOI: 10.1073/pnas.1318172110
Аннотация: Using a systematic, whole-genome analysis of enhancer activity of human-specific endogenous retroviral inserts (hsERVs), we identified an element, hsERVPRODH, that acts as a tissue-specific enhancer for the PRODH gene, which is required for proper CNS functioning. PRODH is one of the candidate genes for susceptibility to schizophrenia and other neurological disorders. It codes for a proline dehydrogenase enzyme, which catalyses the first step of proline catabolism and most likely is involved in neuromediator synthesis in the CNS. We investigated the mechanisms that regulate hsERVPRODH enhancer activity. We showed that the hsERVPRODH enhancer and the internal CpG island of PRODH synergistically activate its promoter. The enhancer activity of hsERVPRODH is regulated by methylation, and in an undermethylated state it can up-regulate PRODH expression in the hippocampus. The mechanism of hsERVPRODH enhancer activity involves the binding of the transcription factor SOX2, whch is preferentially expressed in hippocampus. We propose that the interaction of hsERVPRODH and PRODH may have contributed to human CNS evolution.
Добавил в систему: Балабан Павел Милославович

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Human-specific endogenous retroviral insert serves as an enhancer for the schizophrenia-linked geneстатья

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