Bromodomain testis-specific protein BRDT directs ΔNp63 function and super enhancer activity in a distinct subset of esophageal squamous cell carcinomas [ChIP-seq]. Bromodomain testis-specific protein BRDT directs ΔNp63 function and super enhancer activity in a distinct subset of esophageal squamous cell carcinomas [ChIP-seq]

Using an unbiased method, we found a testis-specific epigenetic reader protein BRDT to be expressed and functional active in a significant portion of ESCC patients. Mechanistically, BRDT co-localizes with ΔNp63, a defining transcription factor for squamous subtype, at selected super-enhancers to regulate ΔNp63-dependent transcription programs to promote cell migration. Pharmacologically depleting BRDT resembles the effects of knock-down of BRDT, thus providing a promising clinical approach for precision medicine in a subset of ESCC. Overall design: Examination of BRDT, BRD4, p63 and various histone modifications in ESCC.

我们采用无偏倚研究方法，发现睾丸特异性表观遗传阅读器蛋白（epigenetic reader protein）BRDT在相当比例的食管鳞状细胞癌（Esophageal Squamous Cell Carcinoma，ESCC）患者体内表达且具备功能活性。从机制层面来看，BRDT与鳞状细胞亚型标志性转录因子ΔNp63共定位至选定的超级增强子区域，通过调控依赖ΔNp63的转录程序以促进细胞迁移。通过药理学手段耗竭BRDT的效果与BRDT基因敲低的效果高度相似，为此类食管鳞状细胞癌亚群的精准医学研究提供了极具前景的临床干预策略。整体实验设计：检测食管鳞状细胞癌样本中BRDT、BRD4、p63的表达情况及多种组蛋白修饰状态。