Gimelbrant Alexander A, Ensminger Alexander W, Qi Peimin, Zucker Jacob, Chess Andrew
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
J Biol Chem. 2005 Jan 14;280(2):1354-9. doi: 10.1074/jbc.M411283200. Epub 2004 Nov 1.
The number of autosomal mammalian genes subject to random monoallelic expression has been limited to genes highly specific to the function of chemosensory neurons or lymphocytes, making this phenomenon difficult to address systematically. Here we demonstrate that asynchronous DNA replication can be used as a marker for the identification of novel genes with monoallelic expression and identify p120 catenin, a gene involved in cell adhesion, as belonging to this class. p120 is widely expressed; its presence in available cell lines allowed us to address quantitative aspects of monoallelic expression. We show that the epigenetic choice of active allele is clonally stable and that biallelic clones express p120 at twice the level of monoallelic clones. Unlike previous reports about genes of this type, we found that expression of p120 can be monoallelic in one cell type and strictly biallelic in another. We show that in human lymphoblasts, the silencing of one allele is incomplete. These unexpected properties are likely to be wide-spread, as we show that the Tlr4 gene shares them. Identification of monoallelic expression of a nearly ubiquitous gene indicates that this type of gene regulation is more common than previously thought. This has important implications for carcinogenesis and definition of cell identity.
随机单等位基因表达的常染色体哺乳动物基因数量一直局限于对化学感应神经元或淋巴细胞功能高度特异的基因，这使得该现象难以系统地研究。在此，我们证明异步DNA复制可作为鉴定具有单等位基因表达的新基因的标志物，并鉴定出参与细胞黏附的基因p120连环蛋白属于此类。p120广泛表达；其在现有细胞系中的存在使我们能够研究单等位基因表达的定量方面。我们表明，活性等位基因的表观遗传选择在克隆上是稳定的，并且双等位基因克隆表达p120的水平是单等位基因克隆的两倍。与先前关于此类基因的报道不同，我们发现p120的表达在一种细胞类型中可以是单等位基因的，而在另一种细胞类型中则严格是双等位基因的。我们表明，在人类淋巴母细胞中，一个等位基因的沉默是不完全的。这些意外特性可能很普遍，因为我们表明Tlr4基因也具有这些特性。鉴定一个几乎普遍存在的基因的单等位基因表达表明，这种类型的基因调控比以前认为的更为常见。这对癌症发生和细胞身份的定义具有重要意义。
