Mahajan Milind C, Narlikar Geeta J, Boyapaty Gokul, Kingston Robert E, Weissman Sherman M
Department of Genetics, The Anlyan Center, Yale University School of Medicine, New Haven, CT 06511, USA.
Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):15012-7. doi: 10.1073/pnas.0507596102. Epub 2005 Oct 10.
Locus control regions (LCRs) are regulatory DNA sequences that are situated many kilobases away from their cognate promoters. LCRs protect transgenes from position effect variegation and heterochromatinization and also promote copy-number dependence of the levels of transgene expression. In this work, we describe the biochemical purification of a previously undescribed LCR-associated remodeling complex (LARC) that consists of heterogeneous nuclear ribonucleoprotein C1/C2, nucleosome remodeling SWI/SNF, and nucleosome remodeling and deacetylating (NuRD)/MeCP1 as a single homogeneous complex. LARC binds to the hypersensitive 2 (HS2)-Maf recognition element (MARE) DNA in a sequence-specific manner and remodels nucleosomes. Heterogeneous nuclear ribonucleoprotein C1/C2, previously known as a general RNA binding protein, provides a sequence-specific DNA recognition element for LARC, and the LARC DNA-recognition sequence is essential for the enhancement of transcription by HS2. Independently of the initiation of transcription, LARC becomes associated with beta-like globin promoters.
位点控制区（LCRs）是位于与其同源启动子相距数千碱基的调控DNA序列。LCRs可保护转基因免受位置效应斑驳和异染色质化影响，还能促进转基因表达水平的拷贝数依赖性。在这项研究中，我们描述了一种先前未描述的与LCR相关的重塑复合体（LARC）的生化纯化过程，该复合体由异质性细胞核核糖核蛋白C1/C2、核小体重塑SWI/SNF以及核小体重塑与去乙酰化（NuRD）/MeCP1组成单一的均一复合体。LARC以序列特异性方式结合超敏2（HS2）-Maf识别元件（MARE）DNA并重塑核小体。异质性细胞核核糖核蛋白C1/C2，以前被认为是一种通用RNA结合蛋白，为LARC提供了序列特异性DNA识别元件，并且LARC的DNA识别序列对于HS2增强转录至关重要。与转录起始无关，LARC与β样珠蛋白启动子相关联。
