論文 - 詳細
| RRC ID | 52164 |
|---|---|
| 著者 | Fukuhara M, Ma Y, Nagasawa K, Toyoshima F. |
| タイトル | A G-quadruplex structure at the 5' end of the H19 coding region regulates H19 transcription. |
| ジャーナル | Sci Rep |
| Abstract |
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. |
| 巻・号 | 8 |
| ページ | 45815 |
| 公開日 | 2017-4-3 |
| DOI | 10.1038/srep45815 |
| PII | srep45815 |
| PMID | 28367967 |
| PMC | PMC5377947 |
| MeSH | Animals Circular Dichroism DNA Methylation / genetics E2F1 Transcription Factor / genetics G-Quadruplexes* Gene Expression Regulation / genetics Genomic Imprinting / genetics* Guanine / metabolism Humans Mice Nucleotide Motifs / genetics* Open Reading Frames / genetics Promoter Regions, Genetic / genetics RNA, Long Noncoding / genetics* Sequence Deletion / genetics Sp1 Transcription Factor / genetics Transcription Initiation Site |
| IF | 3.998 |
| 引用数 | 10 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | OLV2-1(AES0153) |