Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Blood. 2010 Sep 30;116(13):2356-64. doi: 10.1182/blood-2010-03-272252. Epub 2010 Jun 22.
Ldb1 and erythroid partners SCL, GATA-1, and LMO2 form a complex that is required to establish spatial proximity between the β-globin locus control region and gene and for transcription activation during erythroid differentiation. Here we show that Ldb1 controls gene expression at multiple levels. Ldb1 stabilizes its erythroid complex partners on β-globin chromatin, even though it is not one of the DNA-binding components. In addition, Ldb1 is necessary for enrichment of key transcriptional components in the locus, including P-TEFb, which phosphorylates Ser2 of the RNA polymerase C-terminal domain for efficient elongation. Furthermore, reduction of Ldb1 results in the inability of the locus to migrate away from the nuclear periphery, which is necessary to achieve robust transcription of β-globin in nuclear transcription factories. Ldb1 contributes these critical functions at both embryonic and adult stages of globin gene expression. These results implicate Ldb1 as a factor that facilitates nuclear relocation for transcription activation.
Ldb1 与红细胞相关伙伴 SCL、GATA-1 和 LMO2 形成一个复合物，该复合物对于建立β-珠蛋白基因调控区与基因之间的空间接近性以及在红细胞分化过程中的转录激活是必需的。在这里，我们表明 Ldb1 在多个层面上控制基因表达。尽管 Ldb1 不是 DNA 结合成分之一，但它可以稳定其红细胞复合物伙伴在β-珠蛋白染色质上。此外，Ldb1 对于在基因座中富集关键转录成分是必需的，包括 P-TEFb，它磷酸化 RNA 聚合酶 C 末端结构域的 Ser2 以进行有效的延伸。此外，Ldb1 的减少导致基因座无法从核周缘迁移，这对于在核转录工厂中实现β-珠蛋白的强大转录是必需的。Ldb1 在珠蛋白基因表达的胚胎和成人阶段都发挥了这些关键功能。这些结果表明 Ldb1 是促进核易位以激活转录的一个因素。
