Sniezewski Lukasz, Janik Sylwia, Laszkiewicz Agnieszka, Majkowski Michal, Kisielow Pawel, Cebrat Malgorzata
Laboratory of Molecular and Cellular Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland.
Laboratory of Molecular and Cellular Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland; Laboratory of Tumor Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland.
Dev Comp Immunol. 2018 Apr;81:105-115. doi: 10.1016/j.dci.2017.11.013. Epub 2017 Nov 22.
The RAG-1 and RAG-2 genes form a recombinase complex that is indispensable for V(D)J recombination, which generates the diversity of immunoglobulins and T-cell receptors. It is widely accepted that the presence of RAGs in the genomes of jawed vertebrates and other lineages is a result of the horizontal transfer of a mobile genetic element. While a substantial amount of evidence has been gathered that clarifies the nature of the RAG transposon, far less attention has been paid to the genomic site of its integration in various host organisms. In all genomes of the jawed vertebrates that have been studied to date, the RAG genes are located in close proximity to the NWC gene. We have previously shown that the promoter of the murine NWC genes exhibits a bidirectional activity, which may have facilitated the integration and survival of the RAG transposon in the host genome. In this study, we characterise the promoters of the NWC homologues that are present in the representatives of other jawed vertebrates (H. sapiens, X. tropicalis and D. rerio). We show that the features that are characteristic for promoters as the hosts of a successful transposon integration (in terms of the arrangement, bidirectional and constitutive activity and the involvement of the Zfp143 transcription factor in the promoter regulation) are evolutionarily conserved, which indicates that the presence of RAG genes in jawed vertebrates is a direct result of a successful transposon integration into the NWC locus.
RAG-1和RAG-2基因形成一种重组酶复合物,这对于V(D)J重组是必不可少的,而V(D)J重组产生了免疫球蛋白和T细胞受体的多样性。人们普遍认为,有颌脊椎动物和其他谱系基因组中RAGs的存在是一种可移动遗传元件水平转移的结果。虽然已经收集了大量证据阐明RAG转座子的性质,但对于其在各种宿主生物中整合的基因组位点却很少受到关注。在迄今为止研究过的所有有颌脊椎动物基因组中,RAG基因都位于紧邻NWC基因的位置。我们之前已经表明,小鼠NWC基因的启动子具有双向活性,这可能促进了RAG转座子在宿主基因组中的整合和存活。在这项研究中,我们对其他有颌脊椎动物(智人、热带爪蟾和斑马鱼)代表中存在的NWC同源物的启动子进行了表征。我们表明,作为成功转座子整合宿主的启动子所具有的特征(就排列、双向和组成型活性以及Zfp143转录因子参与启动子调控而言)在进化上是保守的,这表明有颌脊椎动物中RAG基因的存在是转座子成功整合到NWC基因座的直接结果。