Yeganeh Meghdad, Praz Viviane, Cousin Pascal, Hernandez Nouria
Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland.
Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
Genes Dev. 2017 Feb 15;31(4):413-421. doi: 10.1101/gad.293324.116. Epub 2017 Mar 13.
Overlapping gene arrangements can potentially contribute to gene expression regulation. A mammalian interspersed repeat (MIR) nested in antisense orientation within the first intron of the gene, encoding an RNA polymerase III (Pol III) subunit, is conserved in mammals and highly occupied by Pol III. Using a fluorescence assay, CRISPR/Cas9-mediated deletion of the MIR in mouse embryonic stem cells, and chromatin immunoprecipitation assays, we show that the MIR affects expression through transcriptional interference. Our study reveals a mechanism by which a Pol II gene can be regulated at the transcription elongation level by transcription of an embedded antisense Pol III gene.
重叠基因排列可能有助于基因表达调控。一个嵌套在编码RNA聚合酶III(Pol III)亚基基因的第一个内含子内的反义方向的哺乳动物散布重复序列(MIR)在哺乳动物中是保守的,并且被Pol III高度占据。通过荧光测定、CRISPR/Cas9介导的小鼠胚胎干细胞中MIR的缺失以及染色质免疫沉淀测定,我们表明MIR通过转录干扰影响基因表达。我们的研究揭示了一种机制,即Pol II基因可以在转录延伸水平上通过嵌入的反义Pol III基因的转录受到调控。