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增强子、编码和非编码转录功能在超保守元件中的混杂。

Promiscuity of enhancer, coding and non-coding transcription functions in ultraconserved elements.

机构信息

Telethon Institute of Genetics and Medicine (TIGEM), via Pietro Castellino 111, 80131 Napoli, Italy.

出版信息

BMC Genomics. 2010 Mar 4;11:151. doi: 10.1186/1471-2164-11-151.


DOI:10.1186/1471-2164-11-151
PMID:20202189
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2847969/
Abstract

BACKGROUND: Ultraconserved elements (UCEs) are highly constrained elements of mammalian genomes, whose functional role has not been completely elucidated yet. Previous studies have shown that some of them act as enhancers in mouse, while some others are expressed in both normal and cancer-derived human tissues. Only one UCE element so far was shown to present these two functions concomitantly, as had been observed in other isolated instances of single, non ultraconserved enhancer elements. RESULTS: We used a custom microarray to assess the levels of UCE transcription during mouse development and integrated these data with published microarray and next-generation sequencing datasets as well as with newly produced PCR validation experiments. We show that a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand. Although the nature of these transcripts remains a mistery, our meta-analysis of RNA-Seq datasets indicates that they are unlikely to be short RNAs and that some of them might encode nuclear transcripts. In the majority of cases this function overlaps with the already established enhancer function of these elements during mouse development. Utilizing several next-generation sequencing datasets, we were further able to show that the level of expression observed in non-exonic UCEs is significantly higher than in random regions of the genome and that this is also seen in other regions which act as enhancers. CONCLUSION: Our data shows that the concurrent presence of enhancer and transcript function in non-exonic UCE elements is more widespread than previously shown. Moreover through our own experiments as well as the use of next-generation sequencing datasets, we were able to show that the RNAs encoded by non-exonic UCEs are likely to be long RNAs transcribed from only one DNA strand.

摘要

背景:超保守元件(UCEs)是哺乳动物基因组中高度约束的元件,其功能作用尚未完全阐明。先前的研究表明,它们中的一些在小鼠中作为增强子发挥作用,而另一些则在正常和癌症衍生的人类组织中表达。迄今为止,只有一个 UCE 元件表现出这两种功能,就像在其他孤立的非超保守增强子元件的实例中观察到的那样。

结果:我们使用定制的微阵列来评估 UCE 在小鼠发育过程中的转录水平,并将这些数据与已发表的微阵列和下一代测序数据集以及新产生的 PCR 验证实验进行整合。我们表明,在检查的所有发育阶段,大量非外显子 UCE 仅从一条 DNA 链转录。尽管这些转录本的性质仍然是个谜,但我们对 RNA-Seq 数据集的荟萃分析表明,它们不太可能是短 RNA,并且其中一些可能编码核转录本。在大多数情况下,这种功能与这些元件在小鼠发育过程中已经建立的增强子功能重叠。利用几种下一代测序数据集,我们还能够表明在非外显子 UCE 中观察到的表达水平明显高于基因组中随机区域的表达水平,并且在其他作为增强子的区域也观察到这种情况。

结论:我们的数据表明,非外显子 UCE 元件中增强子和转录功能的同时存在比以前显示的更为广泛。此外,通过我们自己的实验以及使用下一代测序数据集,我们能够表明非外显子 UCE 编码的 RNA 很可能是仅从一条 DNA 链转录的长 RNA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eef/2847969/20b767a29886/1471-2164-11-151-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eef/2847969/c3d06d679e61/1471-2164-11-151-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eef/2847969/6d93dd181d16/1471-2164-11-151-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eef/2847969/c5b0c96ed5d0/1471-2164-11-151-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eef/2847969/a802a8909c3a/1471-2164-11-151-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eef/2847969/20b767a29886/1471-2164-11-151-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eef/2847969/c3d06d679e61/1471-2164-11-151-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eef/2847969/6d93dd181d16/1471-2164-11-151-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eef/2847969/c5b0c96ed5d0/1471-2164-11-151-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eef/2847969/a802a8909c3a/1471-2164-11-151-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5eef/2847969/20b767a29886/1471-2164-11-151-5.jpg

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[6]
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[5]
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[6]
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[7]
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[8]
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[9]
The most deeply conserved noncoding sequences in plants serve similar functions to those in vertebrates despite large differences in evolutionary rates.

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[10]
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本文引用的文献

[1]
ChIP-seq accurately predicts tissue-specific activity of enhancers.

Nature. 2009-2-12

[2]
Long non-coding RNAs: insights into functions.

Nat Rev Genet. 2009-3

[3]
Ultraconserved elements: genomics, function and disease.

RNA Biol. 2008

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Genomics. 2008-10

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Nat Methods. 2008-7

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Ultraconservation identifies a small subset of extremely constrained developmental enhancers.

Nat Genet. 2008-2

[8]
Large-scale appearance of ultraconserved elements in tetrapod genomes and slowdown of the molecular clock.

Mol Biol Evol. 2008-2

[9]
Deletion of ultraconserved elements yields viable mice.

PLoS Biol. 2007-9

[10]
Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas.

Cancer Cell. 2007-9

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