Herrscher R F, Kaplan M H, Lelsz D L, Das C, Scheuermann R, Tucker P W
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235-9048, USA.
Genes Dev. 1995 Dec 15;9(24):3067-82. doi: 10.1101/gad.9.24.3067.
B lymphocyte-restricted transcription of immunoglobulin heavy-chain (IgH) genes is specified by elements within the variable region (VH) promoter and the intronic enhancer (E mu). The gene encoding a protein that binds a VH promoter proximal site necessary for induced mu-heavy-chain transcription has been cloned. This B-cell specific protein, termed Bright (B cell regulator of IgH transcription), is found in both soluble and matrix insoluble nuclear fractions. Bright binds the minor groove of a restricted ATC sequence that is sufficient for nuclear matrix association. This sequence motif is present in previously described matrix-associating regions (MARs) proximal to the promoter and flanking E mu. Bright can activate E mu-driven transcription by binding these sites, but only when they occur in their natural context and in cell lines permissive for E mu activity. To bind DNA, Bright requires a novel tetramerization domain and a previously undescribed domain that shares identity with several proteins, including SWI1, a component of the SWI/SNF complex.
免疫球蛋白重链(IgH)基因的B淋巴细胞限制性转录由可变区(VH)启动子和内含子增强子(Eμ)中的元件决定。编码一种结合诱导μ重链转录所需的VH启动子近端位点的蛋白质的基因已被克隆。这种B细胞特异性蛋白,称为Bright(IgH转录的B细胞调节因子),存在于可溶性和核基质不溶性核组分中。Bright结合一个有限的ATC序列的小沟,该序列足以与核基质结合。这个序列基序存在于先前描述的启动子近端和Eμ侧翼的基质结合区域(MARs)中。Bright可以通过结合这些位点来激活Eμ驱动的转录,但只有当它们出现在其自然环境中以及对Eμ活性允许的细胞系中时才行。为了结合DNA,Bright需要一个新的四聚化结构域和一个与几种蛋白质具有同源性的先前未描述的结构域,包括SWI/SNF复合物的一个组分SWI1。