Assaying the regulatory potential of mammalian conserved non-coding sequences in human cells.
Assaying the regulatory potential of mammalian conserved non-coding sequences in human cells.
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DOI：
10.1186/gb-2008-9-12-r168
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发表时间：
2008
期刊：
影响因子：
12.3
通讯作者：
Stamatoyannopoulos JA
中科院分区：
文献类型：
--
作者：
Attanasio C;Reymond A;Humbert R;Lyle R;Kuehn MS;Neph S;Sabo PJ;Goldy J;Weaver M;Haydock A;Lee K;Dorschner M;Dermitzakis ET;Antonarakis SE;Stamatoyannopoulos JA
在任何给定的细胞类型中，实验活性保守非编码序列的分数都很低，因此经典测定不太可能暴露其潜力。人类基因组中保守的非编码序列比已知基因的丰度高出约10倍，并且已经被假设为标记顺式调控元件的位置。然而，保守的非编码序列对人类基因转录调控的整体贡献目前尚不清楚。人类和硬骨鱼之间共享的高度保守的元件主要是在形态发生期间活跃的侧翼基因，并且富含正转录调控元件。然而，这种高度保守的元件占人类基因组中保守非编码序列的<1%，其主要是哺乳动物。我们探索了这些“常见的”保守的非编码序列的大样本的监管潜力，使用各种经典的测定，包括染色质重塑，增强子/抑制子和启动子活性。当在不同的人类模型细胞类型中进行测试时，我们发现任何给定细胞类型中实验活性保守非编码序列的比例都很低（约5%），并且当在细胞类型中共同考虑时，这一比例仅适度增加。结果表明，经典的顺式调节潜力的测定不太可能暴露人类基因组中绝大多数哺乳动物保守的非编码序列的功能潜力。
The fraction of experimentally active conserved non-coding sequences within any given cell type is low, so classical assays are unlikely to expose their potential. Conserved non-coding sequences in the human genome are approximately tenfold more abundant than known genes, and have been hypothesized to mark the locations of cis-regulatory elements. However, the global contribution of conserved non-coding sequences to the transcriptional regulation of human genes is currently unknown. Deeply conserved elements shared between humans and teleost fish predominantly flank genes active during morphogenesis and are enriched for positive transcriptional regulatory elements. However, such deeply conserved elements account for <1% of the conserved non-coding sequences in the human genome, which are predominantly mammalian. We explored the regulatory potential of a large sample of these 'common' conserved non-coding sequences using a variety of classic assays, including chromatin remodeling, and enhancer/repressor and promoter activity. When tested across diverse human model cell types, we find that the fraction of experimentally active conserved non-coding sequences within any given cell type is low (approximately 5%), and that this proportion increases only modestly when considered collectively across cell types. The results suggest that classic assays of cis-regulatory potential are unlikely to expose the functional potential of the substantial majority of mammalian conserved non-coding sequences in the human genome.
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影响因子：
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作者：
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