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药物破坏基因组结合位点可重塑PU.1先驱转录因子的活性—小柯机器人—科学网
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K., Steidl, Ulrich</p> <p> Issue&Volume: 2024-09-18</p> <p> Abstract: Transcription factor (TF) DNA-binding dynamics govern cell fate and identity. However, our ability to pharmacologically control TF localization is limited. Here we leverage chemically driven binding site restriction leading to robust and DNA-sequence-specific redistribution of PU.1, a pioneer TF pertinent to many hematopoietic malignancies. Through an innovative technique, ‘CLICK-on-CUT&Tag’, we characterize the hierarchy of de novo PU.1 motifs, predicting occupancy in the PU.1 cistrome under binding site restriction. Temporal and single-molecule studies of binding site restriction uncover the pioneering dynamics of native PU.1 and identify the paradoxical activation of an alternate target gene set driven by PU.1 localization to second-tier binding sites. These transcriptional changes were corroborated by genetic blockade and site-specific reporter assays. Binding site restriction and subsequent PU.1 network rewiring causes primary human leukemia cells to differentiate. In summary, pharmacologically induced TF redistribution can be harnessed to govern TF localization, actuate alternate gene networks and direct cell fate.</p> <p> DOI: 10.1038/s41588-024-01911-7</p> <p> Source: <a href="https://www.nature.com/articles/s41588-024-01911-7">https://www.nature.com/articles/s41588-024-01911-7</a></p> </p> <div class="remarks">期刊信息</div> <div class="dd"><p> <span style="font-weight: bold;">Nature Genetics：</span>《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307<br /> <span style="font-weight: bold;">官方网址：</span><a href="https://www.nature.com/ng/" target="_blank">https://www.nature.com/ng/</a><br /> <span style="font-weight: bold;">投稿链接：</span><a href="https://mts-ng.nature.com/cgi-bin/main.plex" target="_blank">https://mts-ng.nature.com/cgi-bin/main.plex</a></p> </div> </div> </div> <style> #footer{ background:#890f0e; text-align:center; padding:10px; color:#FFF; font-size:12px;} #footer a{color:#FFF; font-size:12px;} </style> <div id="footer"><a href="http://www.sciencenet.cn/aboutus/" target="_blank">关于我们</a> | <a href="http://www.sciencenet.cn/shengming.aspx" target="_blank">网站声明</a> | <a href="http://www.sciencenet.cn/tiaokuang.aspx" target="_blank">服务条款</a> | <a href="http://www.sciencenet.cn/contact.aspx" target="_blank">联系方式</a> | <a href="http://www.sciencenet.cn/RSS.aspx">RSS</a> | <a href="mailto:jubao@stimes.cn">举报</a> | <a href="https://stimes.sciencenet.cn/">中国科学报社</a> <br> <a href="https://beian.miit.gov.cn" target="_blank" > 京ICP备07017567号-12 </a> 互联网新闻信息服务许可证10120230008 京公网安备 11010802032783<br>Copyright @ 2007-<script type="text/javascript">var Date22 = new Date();var year22 = Date22.getFullYear();document.write(year22);</script> 中国科学报社 All Rights Reserved<br> 地址：北京市海淀区中关村南一条乙三号 邮箱：blog@stimes.cn <br> <span style="display:none"> <script type="text/javascript"> var _bdhmProtocol = (("https:" == document.location.protocol) ? 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