首页> 外文期刊>Genomics >Comparative and functional analyses of LYL1 loci establish marsupial sequences as a model for phylogenetic footprinting( small star, filled ).
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Comparative and functional analyses of LYL1 loci establish marsupial sequences as a model for phylogenetic footprinting( small star, filled ).

机译:LYL1基因座的比较和功能分析建立了有袋序列作为系统发育足迹的模型(小星,实心)。

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Comparative genomic sequence analysis is a powerful technique for identifying regulatory regions in genomic DNA. However, its utility largely depends on the evolutionary distances between the species involved. Here we describe the screening of a genomic BAC library from the stripe-faced dunnart, Sminthopsis macroura, formerly known as the narrow-footed marsupial mouse. We isolated a clone containing the LYL1 locus, completely sequenced the 60.6-kb insert, and compared it with orthologous human and mouse sequences. Noncoding homology was substantially reduced in the human/dunnart analysis compared with human/mouse, yet we could readily identify all promoters and exons. Human/mouse/dunnart alignments of the LYL1 candidate promoter allowed us to identify putative transcription factor binding sites, revealing a pattern highly reminiscent of critical regulatory regions of the LYL1 paralogue, SCL. This newly identified LYL1 promoter showed strong activity in myeloid progenitor cells and was bound in vivo by Fli1, Elf1, and Gata2-transcription factors all previously shown to bind to the SCL stem cell enhancer. This study represents the first large-scale comparative analysis involving marsupial genomic sequence and demonstrates that such comparisons provide a powerful approach to characterizing mammalian regulatory elements.
机译:比较基因组序列分析是一种用于鉴定基因组DNA中调控区域的强大技术。但是,其效用很大程度上取决于所涉及物种之间的进化距离。在这里,我们描述了从条纹状邓纳氏菌(Sminthopsis macroura)(原名窄脚有袋小鼠)中筛选基因组BAC文库的方法。我们分离了一个包含LYL1基因座的克隆,对60.6-kb的插入片段进行了完全测序,并将其与直系同源的人和小鼠序列进行了比较。与人/小鼠相比,人/ dunnart分析中的非编码同源性显着降低,但我们可以轻松识别所有启动子和外显子。 LYL1候选启动子的人/小鼠/ Dunnart比对使我们能够识别推定的转录因子结合位点,从而揭示出一种模式,非常让人联想到LYL1旁系同源物SCL的关键调控区。这个新发现的LYL1启动子在髓样祖细胞中显示出强大的活性,并在体内被Fli1,Elf1和Gata2转录因子体内结合,这些因子先前均显示与SCL干细胞增强剂结合。这项研究代表了涉及有袋动物基因组序列的首次大规模比较分析,并证明这种比较提供了表征哺乳动物调节元件的有力方法。

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