A robust characterization of retinoic acid response elements based on a comparison of sites in three species

A robust characterization of retinoic acid response elements based on a comparison of sites in three species
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DOI:
10.1016/j.jsbmb.2005.05.005
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发表时间:
2005-09-01
影响因子:
4.1
通讯作者:
Blomhoff, R
Blomhoff, R
中科院分区:
生物学2区
文献类型:
--
作者:
Balmer, JE;Blomhoff, R

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高通量基因组测序的可用性使我们能够构建比过去更可靠的视黄酸反应元件特征。我们找到了 51 个有据可查的保守视黄酸反应元件中每一个的人类、小鼠和大鼠同源物。对这 153 个位点(其中 78 个是新位点)的数学和统计分析表明,92% 的响应元素具有直接重复对称性,但只有 76% 表现出规范间距属性。虽然维持了 Farniliar 的“(a/g)g(g/t)tca”六聚体基序,但更宽松的序列“(a/g)g(g/t)(g/t)(g/c)a”代表了 10% 的共识。位点位于编码链和非编码链上的可能性相同,其中 86% 位于上游位置。从统计的角度来看,DR1 元素与 DR2 和 DR5 元素有根本的不同,但这仅在 5' 六角体中明显不同。虽然核心位置存在相当大的变化,并且在任何位置都不能认为核苷酸是被禁止的,但一旦获得功能位点,固定基因座上的物种之间的变化似乎令人惊讶地受到限制。 (c) 2005 Elsevier Ltd. 保留所有权利。
The availability of high-throughput genomic sequencing has allowed us to construct a more robust characterization of retinoic acid response elememts than was possible in the past. We located human, mouse, and rat homologs for each of 51 well-documented, conserved retinoic acid response elements. Mathematical and statistical analyses of these 153 sites, 78 of which are new, shows that 92% of response elements have direct-repeat symmetry, but that only 76% exhibit canonical spacing attributes. While the farniliar '(a/g)g(g/t)tca' hexamer motif is upheld, the more relaxed sequence, '(a/g)g(g/t)(g/t)(g/c)a', represents a 10% consensus. Sites are as likely to be on the coding strand as on the non-coding strand, and 86% of them are in upstream locations. From a statistical point of view, DR1 elements are fundamentally different from DR2 and DR5 elements, but this is only evident in the 5' hexarner. While there is considerable variation in core positions, and while no nucleotide can be considered forbidden at any position, variation among species at a fixed locus appears surprisingly constrained once a functional site has been attained. (c) 2005 Elsevier Ltd. All rights reserved.