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ePIP–HoGu, A Cooperative DNA Binding System to Recruit Epigenetic Modifier to the Targeted DNA Locus

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Part of the Springer Theses book series (Springer Theses)

Abstract

Synthetic DNA-based epi-drugs mimicking the cooperative function of natural transcription factor pairs are in demand owing to their flexible gap distance, favorable sequence selectivity, and wide biological applications. Here, we detail the development of the a epigenetically active cooperative DNA binding platform assisted by Cucurbit[7]uril (CB7) host–guest modules (ePIP–HoGu) that not only mimic the operation of their natural counterparts as pairs but are also capable of recruiting the epigenetic modifiers to a particular DNA locus. A CB7-assisted cooperative DNA binding system demonstrated superior cooperativity and versatility over its conventional counterpart, especially for the situation of long spacing, long PIP length, and flexible binding orientation. The in vitro HAT-ChIP-PCR assay validated in vitro that ePIP–HoGu could remarkably recruit epi-enzyme modulator to the target sequence with DNA repeat binding sites, resulting in proximate histone acetylation. Our synthetic approach suggests the potential of delivering epi-drugs precisely and activating genes on demand.

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Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Department of Chemistry, Graduate School of ScienceKyoto UniversityKyotoJapan

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