Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, United States of America.
Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, United States of America.
Biochim Biophys Acta Gene Regul Mech. 2019 Jun;1862(6):625-633. doi: 10.1016/j.bbagrm.2019.04.003. Epub 2019 Apr 22.
The eukaryotic genome is organized at varying levels into chromosome territories, transcriptional compartments and topologically associating domains (TADs), which are architectural features largely shared between different cell types and across species. In contrast, within TADs, chromatin loops connect enhancers and their target genes to establish unique transcriptomes that distinguish cells and tissues from each other and underlie development and differentiation. How these tissue-specific and temporal stage-specific long-range contacts are formed and maintained is a fundamental question in biology. The widely expressed Lim domain binding 1 protein, LDB1, plays a critical role in connecting enhancers and genes by forming complexes with cell-type specificity across diverse developmental pathways including neurogenesis, cardiogenesis, retinogenesis and hematopoiesis. Here we review the multiple roles of LDB1 in cell fate determination and in chromatin loop formation, with an emphasis on mammalian systems, to illuminate how LDB1 functions in normal cells and in diseases such as cancer.
真核基因组在不同层次上组织成染色体区域、转录隔室和拓扑关联域 (TAD)，这些结构特征在不同细胞类型和物种之间广泛共享。相比之下，在 TAD 内，染色质环连接增强子及其靶基因，以建立独特的转录组，将细胞和组织彼此区分开来，并为发育和分化提供基础。这些组织特异性和时间特异性长程接触是如何形成和维持的，是生物学中的一个基本问题。广泛表达的 Lim 结构域结合蛋白 1（LDB1）通过与包括神经发生、心脏发生、视网膜发生和造血在内的多种发育途径中的细胞类型特异性形成复合物，在连接增强子和基因方面发挥着关键作用。本文综述了 LDB1 在细胞命运决定和染色质环形成中的多种作用，重点介绍了哺乳动物系统，以阐明 LDB1 在正常细胞以及癌症等疾病中的功能。
