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タイトル: | Massively parallel reporter perturbation assays uncover temporal regulatory architecture during neural differentiation |
著者: | Kreimer, Anat Ashuach, Tal Inoue, Fumitaka https://orcid.org/0000-0003-0657-434X (unconfirmed) Khodaverdian, Alex Deng, Chengyu Yosef, Nir Ahituv, Nadav |
著者名の別形: | 井上, 詞貴 |
キーワード: | Computational biology and bioinformatics Differentiation Functional genomics Gene regulation Neural stem cells |
発行日: | 2022 |
出版者: | Springer Nature |
誌名: | Nature Communications |
巻: | 13 |
論文番号: | 1504 |
抄録: | Gene regulatory elements play a key role in orchestrating gene expression during cellular differentiation, but what determines their function over time remains largely unknown. Here, we perform perturbation-based massively parallel reporter assays at seven early time points of neural differentiation to systematically characterize how regulatory elements and motifs within them guide cellular differentiation. By perturbing over 2, 000 putative DNA binding motifs in active regulatory regions, we delineate four categories of functional elements, and observe that activity direction is mostly determined by the sequence itself, while the magnitude of effect depends on the cellular environment. We also find that fine-tuning transcription rates is often achieved by a combined activity of adjacent activating and repressing elements. Our work provides a blueprint for the sequence components needed to induce different transcriptional patterns in general and specifically during neural differentiation. |
記述: | 神経細胞を作る遺伝子制御の構造を解明. 京都大学プレスリリース. 2022-03-24. Hundreds of gene regulatory motifs cooperate and conflict to make brain cells. 京都大学プレスリリース. 2022-03-24. |
著作権等: | © The Author(s) 2022 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. |
URI: | http://hdl.handle.net/2433/269001 |
DOI(出版社版): | 10.1038/s41467-022-28659-0 |
PubMed ID: | 35315433 |
関連リンク: | https://ashbi.kyoto-u.ac.jp/ja/news/20220324_research-result_inoue/ https://ashbi.kyoto-u.ac.jp/news/20220324_research-result_inoue/ |
出現コレクション: | 学術雑誌掲載論文等 |
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