Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon.
Brenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, Oregon.
Cancer Res. 2024 Jul 15;84(14):2227-2228. doi: 10.1158/0008-5472.CAN-24-1376.
MYC is an oncogenic transcription factor that binds gene promoters to facilitate oncogenic gene expression. When overexpressed, as is the case in most human cancers, MYC also invades active enhancers-cis-regulatory elements that are critical for regulating gene expression. In previous studies, the regulatory significance of MYC enhancer invasion in cancer cells has been debated. In their study published in Nature Genetics, Jakobsen and colleagues establish a new role for MYC in enhancer regions: regulating cancer type-specific gene programs. Their work reveals a mechanism in which MYC cooperates with other oncogenic transcription factors to recruit epigenetic regulators to enhancers, resulting in an epigenetic "switch" that promotes enhancer activation through BRD4 and RNA polymerase II. This activity was highly cancer-type specific, highlighting gene expression programs that predicted clinical outcome in a subtype-specific manner in patients with breast cancer.
MYC 是一种致癌转录因子，它与基因启动子结合，促进致癌基因的表达。在大多数人类癌症中，MYC 过度表达，也会侵入活跃的增强子——顺式调控元件，这些元件对于调节基因表达至关重要。在之前的研究中，MYC 增强子入侵在癌细胞中的调控意义一直存在争议。在他们发表在《自然遗传学》杂志上的研究中，Jakobsen 及其同事确立了 MYC 在增强子区域的新作用：调节癌症特异性基因程序。他们的工作揭示了一种机制，即 MYC 与其他致癌转录因子合作，招募表观遗传调节剂到增强子，从而形成一种表观遗传“开关”，通过 BRD4 和 RNA 聚合酶 II 促进增强子的激活。这种活性具有高度的癌症类型特异性，突出了以亚组特异性方式预测乳腺癌患者临床结局的基因表达程序。
