Denis Gerald V
Cancer Research Center, Boston University School of Medicine, 72 East Concord Street, K520, Boston, Massachusetts 02118, USA.
Discov Med. 2010 Dec;10(55):489-99.
Double bromodomain proteins bind to acetylated lysines in histones, bringing associated histone modification and nucleosome remodeling activity to chromatin. The ability of bromodomain regulators to alter chromatin status and control gene expression has long been appreciated to be important in the development of certain human cancers. However, bromodomain proteins have now been found also to be critical, non-redundant players in diverse, non-malignant phenotypes, directing transcriptional programs that control adipogenesis, energy metabolism and inflammation. The fact that such different processes are functionally linked by the same molecular machinery suggests a common epigenetic basis to understand and interpret the origins of several important co-morbidities, such as asthma or cancer that occurs in obesity, and complex inflammatory diseases like cardiovascular disease, systemic lupus erythematosus, rheumatoid arthritis and insulin resistance that may be built on a common pro-inflammatory foundation.
双溴结构域蛋白与组蛋白中的乙酰化赖氨酸结合，将相关的组蛋白修饰和核小体重塑活性带到染色质上。长期以来，人们一直认为溴结构域调节剂改变染色质状态和控制基因表达的能力在某些人类癌症的发展中很重要。然而，现在发现溴结构域蛋白在多种非恶性表型中也是关键的、非冗余的参与者，指导着控制脂肪生成、能量代谢和炎症的转录程序。这样不同的过程由相同的分子机制在功能上联系起来，这一事实表明存在一个共同的表观遗传基础，以理解和解释几种重要合并症的起源，比如肥胖症中出现的哮喘或癌症，以及像心血管疾病、系统性红斑狼疮、类风湿性关节炎和胰岛素抵抗等可能建立在共同促炎基础上的复杂炎症性疾病。
