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引用次数: 0
摘要
癌症经常通过利用正常发育过程中的特异性转录因子(TFs)来维持增殖。然而,这些转录因子对肿瘤发生的影响在很大程度上取决于它们在基因组中的结合位点。泰勒及其同事的一篇新论文扩展了之前开发的二脒化合物,这些化合物阻碍了急性髓性白血病(AML)中先锋转录因子 PU.1 (SPI1)的 DNA 结合位点。对这些化合物靶向的基因组 DNA 进行固定和测序后发现,这些抑制剂改变了 PU.1 的基因组结合模式。作者报告说,他们的策略限制了 PU.1 的基因组结合偏好,导致 PU.1 重新分布到启动子和其他 G/C 含量升高的基因近端区域。在此,我们讨论了在血液恶性肿瘤中靶向 PU.1 的最新进展。我们还探讨了 PU.1 和 SWI/SNF ATP 依赖性染色质重塑复合物的共同功能作用,它们共同维持肿瘤细胞增殖所需的增强子景观,但在非肿瘤环境中也有关键作用。
Pharmacological blockade of a pioneer transcription factor.
Cancers frequently co-opt lineage-specific transcription factors (TFs) utilized in normal development to sustain proliferation. However, the effects of these TFs on tumor development depend considerably on where in the genome they bind. A new paper by Taylor and colleagues expands on previously developed diamidine compounds that obstruct the DNA binding sites of the pioneer TF PU.1 (SPI1) in acute myeloid leukemia (AML). Immobilization and sequencing of genomic DNA targeted by these compounds revealed that these inhibitors alter the genomic binding patterns of PU.1. The authors report that their strategy constrains the genomic binding preferences of PU.1, leading to redistribution of PU.1 to promoters and other gene-proximal regions with elevated G/C content. Here we discuss recent developments for targeting PU.1 in hematologic malignancies. We also explore the shared functional roles of PU.1 and SWI/SNF ATP-dependent chromatin remodeling complexes, which work together to sustain the enhancer landscape needed for tumor cell proliferation but also have key roles in non-tumor settings.
期刊介绍:
Cancer Research, published by the American Association for Cancer Research (AACR), is a journal that focuses on impactful original studies, reviews, and opinion pieces relevant to the broad cancer research community. Manuscripts that present conceptual or technological advances leading to insights into cancer biology are particularly sought after. The journal also places emphasis on convergence science, which involves bridging multiple distinct areas of cancer research.
With primary subsections including Cancer Biology, Cancer Immunology, Cancer Metabolism and Molecular Mechanisms, Translational Cancer Biology, Cancer Landscapes, and Convergence Science, Cancer Research has a comprehensive scope. It is published twice a month and has one volume per year, with a print ISSN of 0008-5472 and an online ISSN of 1538-7445.
Cancer Research is abstracted and/or indexed in various databases and platforms, including BIOSIS Previews (R) Database, MEDLINE, Current Contents/Life Sciences, Current Contents/Clinical Medicine, Science Citation Index, Scopus, and Web of Science.