Analysis of variation at transcription factor binding sites in Drosophila and humans.
Analysis of variation at transcription factor binding sites in Drosophila and humans.
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DOI：
10.1186/gb-2012-13-9-r49
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发表时间：
2012-09-28
期刊：
影响因子：
12.3
通讯作者：
Birney E
中科院分区：
文献类型：
--
作者：
Spivakov M;Akhtar J;Kheradpour P;Beal K;Girardot C;Koscielny G;Herrero J;Kellis M;Furlong EE;Birney E
测序技术的进步促进了群体基因组学的发展，并使高精度转录因子结合位点 (TFBS) 的位置定位成为可能。在这里，我们通过将 ENCODE、modENCODE、我们之前发布的数据和其他来源生成的转录因子结合图谱与人类个体和果蝇同基因系的基因组变异数据相结合来研究 TFBS 变异性。我们引入了一种 TFBS 变异性度量，该度量考虑了与突变相关的基序匹配的变化，并使逐个实例以及共享共同生物学特性的集合中的 TFBS 功能约束研究成为可能。我们还利用新出现的每个个体转录因子结合数据来证明 TFBS 突变，特别是在进化保守位点处，可以有效缓冲，以确保转录因子结合的一致水平。我们的分析提供了对个体和种间变异之间关系的见解，并提供了人类和果蝇中 TFBS 突变功能缓冲的证据。从更广泛的角度来看，这些结果证明了结合功能基因组学和群体遗传学方法来理解基因调控的潜力。
Advances in sequencing technology have boosted population genomics and made it possible to map the positions of transcription factor binding sites (TFBSs) with high precision. Here we investigate TFBS variability by combining transcription factor binding maps generated by ENCODE, modENCODE, our previously published data and other sources with genomic variation data for human individuals and Drosophila isogenic lines. We introduce a metric of TFBS variability that takes into account changes in motif match associated with mutation and makes it possible to investigate TFBS functional constraints instance-by-instance as well as in sets that share common biological properties. We also take advantage of the emerging per-individual transcription factor binding data to show evidence that TFBS mutations, particularly at evolutionarily conserved sites, can be efficiently buffered to ensure coherent levels of transcription factor binding. Our analyses provide insights into the relationship between individual and interspecies variation and show evidence for the functional buffering of TFBS mutations in both humans and flies. In a broad perspective, these results demonstrate the potential of combining functional genomics and population genetics approaches for understanding gene regulation.
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影响因子：
4.5
作者：
Hare, Emily E.;Peterson, Brant K.;Iyer, Venky N.;Meier, Rudolf;Eisen, Michael B.
通讯作者：
Eisen, Michael B.
影响因子：
4
作者：
Barolo, Scott
通讯作者：
Barolo, Scott
影响因子：
64.5
作者：
Hallikas, O;Palin, K;Taipale, J
通讯作者：
Taipale, J
DOI：
10.1007/bf02984069
发表时间：
1957-01-01
期刊：
JOUR GENETICS
影响因子：
--
作者：
HALDANE, J. B. S.
通讯作者：
HALDANE, J. B. S.
影响因子：
64.5
作者：
Junion, Guillaume;Spivakov, Mikhail;Furlong, Eileen E. M.
通讯作者：
Furlong, Eileen E. M.