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タイトル: | A G-quadruplex structure at the 5′ end of the H19 coding region regulates H19 transcription |
著者: | Fukuhara, Mitsuko Ma, Yue Nagasawa, Kazuo Toyoshima, Fumiko |
著者名の別形: | 福原, 充子 豊島, 文子 |
発行日: | 3-Apr-2017 |
出版者: | Springer Nature |
誌名: | Scientific Reports |
巻: | 8 |
論文番号: | 45815 |
抄録: | The H19 gene, one of the best known imprinted genes, encodes a long non-coding RNA that regulates cell proliferation and differentiation. H19 RNA is widely expressed in embryonic tissues, but its expression is restricted in only a few tissues after birth. However, regulation of H19 gene expression remains poorly understood outside the context of genomic imprinting. Here we identified evolutionarily conserved guanine (G)-rich repeated motifs at the 5′ end of the H19 coding region that are consistent with theoretically deduced G-quadruplex sequences. Circular dichroism spectroscopy and electrophoretic mobility shift assays with G-quadruplex-specific ligands revealed that the G-rich motif, located immediately downstream of the transcription start site (TSS), forms a G-quadruplex structure in vitro. By using a series of mutant forms of H19 harboring deletion or G-to-A substitutions, we found that the H19-G-quadruplex regulates H19 gene expression. We further showed that transcription factors Sp1 and E2F1 were associated with the H19-G-quadruplex to either suppress or promote the H19 transcription, respectively. Moreover, H19 expression during differentiation of mouse embryonic stem cells appears to be regulated by a genomic H19 G-quadruplex. These results demonstrate that the G-quadruplex structure immediately downstream of the TSS functions as a novel regulatory element for H19 gene expression. |
著作権等: | © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. |
URI: | http://hdl.handle.net/2433/225266 |
DOI(出版社版): | 10.1038/srep45815 |
PubMed ID: | 28367967 |
出現コレクション: | 学術雑誌掲載論文等 |
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