Arrays of ultraconserved non-coding regions span the loci of key developmental genes in vertebrate genomes.
Arrays of ultraconserved non-coding regions span the loci of key developmental genes in vertebrate genomes.
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DOI：
10.1186/1471-2164-5-99
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发表时间：
2004-12-21
期刊：
影响因子：
4.4
通讯作者：
Lenhard B
中科院分区：
文献类型：
--
作者：
Sandelin A;Bailey P;Bruce S;Engström PG;Klos JM;Wasserman WW;Ericson J;Lenhard B
在进化上保守的同源基因内部或相邻的序列通常作为关键的顺式调控区域。最近的研究已经确定了人类和小鼠之间完全保守的长的非编码区，称为超保守区(UCRs)。在这里，我们关注围绕着参与脊椎动物早期发育的基因的UCR；基因在脊椎动物4.5亿年的进化过程中保存了下来。基于高分辨率检测程序，我们的UCR集合使人们能够对脊椎动物基因组组织和发育重要基因的调控有新的见解。我们发现，高度保守的UCR的基因组位置与编码发育关键调控因子的基因的位置密切相关，与转录因子编码基因的位置相关性尤其强。尤其重要的是，观察到大多数UCR都聚集在它们推定的靶基因周围数百个千碱基的阵列中。这种标志性的签名存在于几个未确定特征的人类基因周围，这些基因被预测为编码具有发育重要性的DNA结合蛋白。结合以前的发现，UCRs的基因组结构表明UCRs是基因表达的重要长程调节器。特殊的序列保守性和簇状结构表明，UCR介导的分子事件比传统的转录因子结合的DNA涉及更大的复杂性。这里提出的高分辨率UCR集合为未来的实验研究提供了丰富的目标序列，以确定在脊椎动物进化过程中保存几乎相同的非编码序列阵列所涉及的生化机制的性质。
Evolutionarily conserved sequences within or adjoining orthologous genes often serve as critical cis-regulatory regions. Recent studies have identified long, non-coding genomic regions that are perfectly conserved between human and mouse, termed ultra-conserved regions (UCRs). Here, we focus on UCRs that cluster around genes involved in early vertebrate development; genes conserved over 450 million years of vertebrate evolution. Based on a high resolution detection procedure, our UCR set enables novel insights into vertebrate genome organization and regulation of developmentally important genes. We find that the genomic positions of deeply conserved UCRs are strongly associated with the locations of genes encoding key regulators of development, with particularly strong positional correlation to transcription factor-encoding genes. Of particular importance is the observation that most UCRs are clustered into arrays that span hundreds of kilobases around their presumptive target genes. Such a hallmark signature is present around several uncharacterized human genes predicted to encode developmentally important DNA-binding proteins. The genomic organization of UCRs, combined with previous findings, suggests that UCRs act as essential long-range modulators of gene expression. The exceptional sequence conservation and clustered structure suggests that UCR-mediated molecular events involve greater complexity than traditional DNA binding by transcription factors. The high-resolution UCR collection presented here provides a wealth of target sequences for future experimental studies to determine the nature of the biochemical mechanisms involved in the preservation of arrays of nearly identical non-coding sequences over the course of vertebrate evolution.
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影响因子：
4.4
作者：
Bagheri-Fam, S;Ferraz, C;Pfeifer, D
通讯作者：
Pfeifer, D
影响因子：
7
作者：
Lifanov, AP;Makeev, VJ;Papatsenko, DA
通讯作者：
Papatsenko, DA
DOI：
10.1073/pnas.112212199
发表时间：
2002-05-28
影响因子：
11.1
作者：
Lettice, LA;Horikoshi, T;Noji, S
通讯作者：
Noji, S
影响因子：
7
作者：
Ghanem, N;Jarinova, O;Ekker, M
通讯作者：
Ekker, M
影响因子：
4.4
作者：
Sabarinadh, C;Subramanian, S;Mishra, RK
通讯作者：
Mishra, RK