Intergenic, gene terminal, and intragenic CpG islands in the human genome.

Intergenic, gene terminal, and intragenic CpG islands in the human genome.
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DOI:
10.1186/1471-2164-11-48
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发表时间:
2010-01-19
期刊:
影响因子:
4.4
通讯作者:
Makeev VJ
Makeev VJ
中科院分区:
生物学2区
文献类型:
--
作者:
Medvedeva YA;Fridman MV;Oparina NJ;Malko DB;Ermakova EO;Kulakovskiy IV;Heinzel A;Makeev VJ

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最近,人们发现人类基因组中含有许多非编码RNA的转录起始位点。与这种非编码RNA的转录相关的调控区域研究很少。这些调控区中的一些可能与位于远离任何蛋白质编码基因的转录起始位点的CpG岛相关。人类基因组包含许多这样的CpG岛;然而,直到现在,它们的特性还没有被系统地研究。本研究运用生物信息学和比较基因组学的方法对人类基因组不同区域的CpG岛进行了研究。我们已经观察到CpG岛具有与外显子重叠的偏好,包括位于远离转录起始位点的外显子,但通常延伸到内含子中。含CpG密码子的同义替换率在CpG岛与蛋白质编码外显子重叠的区域中显著降低,即使它们位于远离转录起始位点的下游。CAGE标签分析显示,在所有的CpG岛,包括那些发现远离蛋白质编码基因的转录起始位点频繁的转录起始位点。对已发表的ChIP芯片数据的计算预测和分析表明,CpG岛包含更多被Sp1蛋白识别的位点。含有更多CAGE标签的CpG岛通常也含有更多的Sp1结合位点。这对于位于3'基因区域的CpG岛尤其相关。在远离任何已知蛋白质编码基因的转录起始位点的富含CAGE的CpG岛中发现了各种转录的实例,这些实例由mRNA或EST证实,但没有蛋白质编码基因的证据。位于远离蛋白质编码基因转录起始位点的CpG岛具有转录起始活性,并显示Sp1结合特性。在与这些岛重叠的外显子中,含CpG密码子的同义替换率降低。这表明这些CpG岛可能参与了一些非编码RNA的转录起始。
Recently, it has been discovered that the human genome contains many transcription start sites for non-coding RNA. Regulatory regions related to transcription of this non-coding RNAs are poorly studied. Some of these regulatory regions may be associated with CpG islands located far from transcription start-sites of any protein coding gene. The human genome contains many such CpG islands; however, until now their properties were not systematically studied. We studied CpG islands located in different regions of the human genome using methods of bioinformatics and comparative genomics. We have observed that CpG islands have a preference to overlap with exons, including exons located far from transcription start site, but usually extend well into introns. Synonymous substitution rate of CpG-containing codons becomes substantially reduced in regions where CpG islands overlap with protein-coding exons, even if they are located far downstream from transcription start site. CAGE tag analysis displayed frequent transcription start sites in all CpG islands, including those found far from transcription start sites of protein coding genes. Computational prediction and analysis of published ChIP-chip data revealed that CpG islands contain an increased number of sites recognized by Sp1 protein. CpG islands containing more CAGE tags usually also contain more Sp1 binding sites. This is especially relevant for CpG islands located in 3' gene regions. Various examples of transcription, confirmed by mRNAs or ESTs, but with no evidence of protein coding genes, were found in CAGE-enriched CpG islands located far from transcription start site of any known protein coding gene. CpG islands located far from transcription start sites of protein coding genes have transcription initiation activity and display Sp1 binding properties. In exons, overlapping with these islands, the synonymous substitution rate of CpG containing codons is decreased. This suggests that these CpG islands are involved in transcription initiation, possibly of some non-coding RNAs.
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