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与人类启动子中的Alu家族重复序列和CpG岛相关的RNA聚合酶II转录调控信号簇。

Clusters of regulatory signals for RNA polymerase II transcription associated with Alu family repeats and CpG islands in human promoters.

作者信息

Oei Shiao-Li, Babich Victor S, Kazakov Vassily I, Usmanova Nadezhda M, Kropotov Andrey V, Tomilin Nikolai V

机构信息

Institute of Biochemistry, Free University of Berlin, Thielallee 63, D-14195, Berlin-Dahlem, Germany.

出版信息

Genomics. 2004 May;83(5):873-82. doi: 10.1016/j.ygeno.2003.11.001.

Abstract

Primate genomes contain a very large number of short interspersed GC-rich repeats of the Alu family, which are abundant in introns and intergenic spacers but also present in 5' flanking regions of genes enriched in binding motifs (BMs) for transcription factors and frequently containing CpG islands. Here we studied whether CpG islands located in promoters of human genes overlap with Alu repeats and with clusters of BMs for the zinc-finger transcription factors Sp1, estrogen receptor alpha, and YY1. The presence of estrogen-response elements in Alu was shown earlier and here we confirm the presence in the consensus Alu sequence of the binding sites for Sp1 and YY1. Analyzing >5000 promoters from the two databases we found that Alu sequences are underrepresented in promoters compared to introns and that approximately 4% of CpG islands located within the -1000 to +200 segments of human promoters overlap with Alu repeats. Although this fraction was found to be lower for proximal segments of promoters (-500 to +100), our results indicate that a significant number (>1000) of all human genes may be controlled by Alu-associated CpG islands. Analysis of clustering of potential BMs for the indicated transcription factors within some promoters also suggests that the Alu family contributed to the evolution of transcription cis-regulatory modules in the human genome. It is important that among Alu sequences overlapping with CpG islands in promoters a large fraction of members of the old Alu subfamilies is found, suggesting extensive retroposon-assisted regulatory genome evolution during the divergence of the primates.

摘要

灵长类动物基因组包含大量短散在富含GC的Alu家族重复序列,这些序列在内含子和基因间隔区中大量存在,但也存在于富含转录因子结合基序(BMs)且常含有CpG岛的基因5'侧翼区域。在此,我们研究了位于人类基因启动子中的CpG岛是否与Alu重复序列以及锌指转录因子Sp1、雌激素受体α和YY1的BMs簇重叠。此前已证明Alu中存在雌激素反应元件,在此我们证实了Sp1和YY1结合位点在Alu共有序列中的存在。分析来自两个数据库的5000多个启动子,我们发现与内含子相比,Alu序列在启动子中的含量较低,并且位于人类启动子-1000至+200片段内的CpG岛中约有4%与Alu重复序列重叠。尽管在启动子近端片段(-500至+100)中这一比例较低,但我们的结果表明,所有人类基因中相当数量(>1000)的基因可能受Alu相关CpG岛的调控。对某些启动子中上述转录因子潜在BMs聚类的分析还表明,Alu家族对人类基因组中转录顺式调控模块的进化有贡献。重要的是,在与启动子中CpG岛重叠的Alu序列中,发现了很大一部分古老Alu亚家族的成员,这表明在灵长类动物分化过程中,反转录转座子广泛辅助了调控基因组的进化。

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