Yannoutsos Nikos, Barreto Vasco, Misulovin Ziva, Gazumyan Anna, Yu Wong, Rajewsky Nikolaus, Peixoto Bernardo R, Eisenreich Thomas, Nussenzweig Michel C
Laboratory of Molecular Immunology, Rockefeller University, New York, New York 10021, USA.
Nat Immunol. 2004 Apr;5(4):443-50. doi: 10.1038/ni1053. Epub 2004 Mar 14.
We have identified a silencer and an antisilencing element that interact at a distance of 85 kilobases to regulate expression of the recombination activating genes Rag1 and Rag2 in thymocytes. Transgenic experiments showed that Rag promoter-proximal cis elements directed tissue-specific expression and that a Runx-dependent intergenic silencer suppressed expression in developing T cells. Deletion of the antisilencing element from the genomic Rag locus unmasked the intergenic silencer and abrogated Rag expression in developing CD4(+)CD8(+) T cells. We speculate that the Rag antisilencing element belongs to a class of cis elements that might be useful for genome diversification by activating genes encoded by otherwise silent transposable elements.
我们已鉴定出一个沉默子和一个反沉默元件，它们在相距85千碱基的位置相互作用，以调节胸腺细胞中重组激活基因Rag1和Rag2的表达。转基因实验表明，Rag启动子近端顺式元件指导组织特异性表达，且一个依赖Runx的基因间沉默子抑制发育中T细胞的表达。从基因组Rag位点删除反沉默元件会暴露基因间沉默子，并消除发育中CD4(+)CD8(+) T细胞中的Rag表达。我们推测，Rag反沉默元件属于一类顺式元件，可能通过激活原本沉默的转座元件所编码的基因，对基因组多样化有用。
