Analysis of regulatory mechanisms of epigenetic gene regulation by a complex of nuclear matrix protein and noncoding RNA

在人类和小鼠中，绝大多数基因组被转录成RNA，产生大量非蛋白质编码RNA。这些非编码 RNA 与染色质修饰复合物结合，被认为可以调节表观遗传基因的表达。在这项研究中，我们对核基质蛋白 hnRNP U 进行了功能分析，该蛋白调节 Xist 的染色体定位，Xist 是一种参与 X 染色体失活的著名非编码 RNA。我们发现hnRNP U还调节非编码RNA（如Kcnq1ot1和Airn）的染色体定位和功能，并且印记位点的等位基因特异性表达在hnRNP U耗尽后受损。我们还对hnRNP U耗尽的细胞进行了全基因组基因表达分析，发现多个等位基因特异性表达也受到干扰。我们发现了一种从等位基因特异性位点表达的新型非编码RNA，其转录本也以单等位基因的方式与染色体相关。

In the human and mouse, vast majority of the genome is transcribed into RNAs, producing a huge number of non protein-coding RNAs. These noncoding RNAs associate with chromatin-modifying complexes, and are assumed to regulate epigenetic gene expression. In this study, we have performed functional analysis of a nuclear matrix protein hnRNP U that regulate chromosomal localization of Xist, a renowned noncoding RNA involved in the X chromosome inactivation. We found that hnRNP U also regulates the chromosomal localization and function of noncoding RNAs such as Kcnq1ot1 and Airn, and the allele-specific expression of the imprinted loci were impaired upon depletion of hnRNP U. We also performed genome-wide gene expression analysis of the hnRNP U depleted cells, and found that multiple allele-specific expression were also disturbed. We found a novel noncoding RNA expressed from the allele-specific locus, and its transcripts were also associated with the chromosome in a mono-allelic manner.