vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RASvavilov-317Research ArticleСтатьиArticlesВЛИЯНИЕ ФЛАНКИРУЮЩИХ ПОСЛЕДОВАТЕЛЬНОСТЕЙ НА ТОЧНОСТЬ РАСПОЗНАВАНИЯ САЙТОВ СВЯЗЫВАНИЯ ТРАНСКРИПЦИОННЫХ ФАКТОРОВEFFECT OF FLANKING SEQUENCES ON THE ACCURACY OF THE RECOGNITION OF TRANSCRIPTION FACTOR BINDING SITESХлебодароваТ. М.KhlebodarovaT. M.tamara@bionet.nsc.ruОщепковД. Ю.OshchepkovD. Yu.tamara@bionet.nsc.ruЛевицкийВ. Г.LevitskyV. G.tamara@bionet.nsc.ruПодколоднаяО. А.PodkolodnayaO. A.tamara@bionet.nsc.ruИгнатьеваЕ. В.IgnatievaE. V.tamara@bionet.nsc.ruАнанькоЕ. А.AnankoE. A.tamara@bionet.nsc.ruСтепаненкоИ. Л.StepanenkoI. L.tamara@bionet.nsc.ruКолчановН. А.KolchanovN. A.tamara@bionet.nsc.ruФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, РоссияРоссияInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaRussian FederationФедеральное государственное бюджетное учреждение науки Институт цитологии и генетики Сибирского отделения Российской академии наук, Новосибирск, Россия Новосибирский национальный исследовательский государственный университет, Новосибирск, РоссияРоссияInstitute of Cytology and Genetics SB RAS, Novosibirsk, Russia Novosibirsk National Research State University, Novosibirsk, RussiaRussian Federation201421012015184/2876886Copyright © Хлебодарова Т.М., Ощепков Д.Ю., Левицкий В.Г., Подколодная О.А., Игнатьева Е.В., Ананько Е.А., Степаненко И.Л., Колчанов Н.А., 20152015Хлебодарова Т.М., Ощепков Д.Ю., Левицкий В.Г., Подколодная О.А., Игнатьева Е.В., Ананько Е.А., Степаненко И.Л., Колчанов Н.А.Khlebodarova T.M., Oshchepkov D.Y., Levitsky V.G., Podkolodnaya O.A., Ignatieva E.V., Ananko E.A., Stepanenko I.L., Kolchanov N.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/317

Развитие in vitro технологий привело к появлению новых экспериментальных данных о связывании белков с ДНК, которые накапливаются в базах данных и используются при исследовании механизмов регуляции экспрессии генов и разработке компьютерных методов распознавания сайтов связывания в геномах про- и эукариот. Однако пока не ясно, насколько in vitro селектированные последовательности отражают истинную структуру природных сайтов связывания транскрипционных факторов (ТФ). С использованием Кульбака–Лейблера критерия расстояний проведено сравнение сходства частотных матриц сайтов связывания ТФ, построенных на основе выборок искусственно селектированных последовательностей и природных сайтов. Показано, что для 80 % ТФ (из числа исследованных) наблюдается высокое сходство коровых последовательностей природных и искусственных сайтов. Для 20 % ТФ их in vitro селектированные последовательности имеют в коровой структуре сайта более широкий спектр допустимых значимых нуклеотидов, не встречающихся среди природных сайтов. Методом весовых матриц проведена оценка оптимальной длины последовательностей ДНК, включающих природные сайты связывания, при которой удается достичь максимальной точности их распознавания. Обнаружено, что примерно для 80 % ТФ (из исследованных) оптимальная для распознавания длина сайта связывания значительно превышает длину коровой последовательности и длину in vitro селектированных сайтов. Выявленные особенности in vitro селектированных сайтов связывания ТФ накладывают определенные ограничения на их использование при разработке компьютерных методов распознавания потенциальных сайтов в геномных последовательностях.

The development of in vitro methods produced new experimental information on protein binding to DNA, which is accumulated in databases and used in studies of mechanisms regulating gene expression and in the development of computer-assisted methods of binding site recognition in pro- and eukaryotic genomes. However, it is still questionable to what extent sequences selected in vitro reflect the actual structures of natural transcription factor (TF) binding sites. The Kullback – Leibler divergence was applied to the comparison of frequency matrices of TF binding sites constructed on samples of artificially selected sequences and natural sites. Core sequences of natural and artificial sites showed high similarity for 80 % of all TFs studied. For 20 % of TFs, binding site sequences selected in vitro had a broader range of permissible significant nucleotides not found in natural sites. The optimum lengths of DNA sequences including natural binding sites, at which they are recognized most accurately, were estimated by the weight matrix method. For approximately 80 % of the TFs studied, the optimum binding site length notably exceeded the lengths of the core sequences, as well as the lengths of in vitro selected sites. The detected features of in vitro selected TF binding sites impose constraints on their use in the development of computer-assisted methods of the recognition of candidate sites in genomic sequences.

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The authors declare that there are no conflicts of interest present.