Mugford Joshua W, Starmer Joshua, Williams Rex L, Calabrese J Mauro, Mieczkowski Piotr, Yee Della, Magnuson Terry
Department of Genetics, Carolina Center for Genome Sciences, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
Department of Genetics, Carolina Center for Genome Sciences, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
Genetics. 2014 Jun;197(2):715-23. doi: 10.1534/genetics.114.162800. Epub 2014 Mar 19.
X chromosome inactivation (XCI) is an epigenetic process that almost completely inactivates one of two X chromosomes in somatic cells of mammalian females. A few genes are known to escape XCI and the mechanism for this escape remains unclear. Here, using mouse trophoblast stem (TS) cells, we address whether particular chromosomal interactions facilitate escape from imprinted XCI. We demonstrate that promoters of genes escaping XCI do not congregate to any particular region of the genome in TS cells. Further, the escape status of a gene was uncorrelated with the types of genomic features and gene activity located in contacted regions. Our results suggest that genes escaping imprinted XCI do so by using the same regulatory sequences as their expressed alleles on the active X chromosome. We suggest a model where regulatory control of escape from imprinted XCI is mediated by genomic elements located in close linear proximity to escaping genes.
X染色体失活（XCI）是一种表观遗传过程，几乎可使哺乳动物雌性体细胞中的两条X染色体之一完全失活。已知有少数基因可逃避XCI，但其逃避机制尚不清楚。在此，我们利用小鼠滋养层干细胞（TS细胞）来研究特定的染色体相互作用是否有助于从印记XCI中逃逸。我们证明，在TS细胞中，逃避XCI的基因启动子不会聚集到基因组的任何特定区域。此外，基因的逃逸状态与其在接触区域中的基因组特征类型和基因活性无关。我们的结果表明，逃避印记XCI的基因是通过使用与活性X染色体上其表达等位基因相同的调控序列来实现的。我们提出了一个模型，其中印记XCI逃逸的调控是由位于与逃逸基因紧密线性相邻位置的基因组元件介导的。
