A sequence level model of an intact locus predicts the location and function of nonadditive enhancers

被引:12
作者
Barr, Kenneth A. [1 ]
Reinitz, John [1 ,2 ,3 ,4 ,5 ]
机构
[1] Univ Chicago, Comm Genet Genom & Syst Biol, Chicago, IL 60637 USA
[2] Univ Chicago, Dept Stat, Chicago, IL 60637 USA
[3] Univ Chicago, Dept Ecol & Evolut, 940 E 57Th St, Chicago, IL 60637 USA
[4] Univ Chicago, Dept Mol Genet & Cell Biol, 920 E 58Th St, Chicago, IL 60637 USA
[5] Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA
关键词
SEGMENTATION GENE-EXPRESSION; TRANSCRIPTION FACTOR-BINDING; CIS-REGULATORY MODULES; MULTIPLE ENHANCERS; SHADOW ENHANCERS; COMMON SET; DROSOPHILA; STRIPE; ELEMENTS; PATTERNS;
D O I
10.1371/journal.pone.0180861
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Metazoan gene expression is controlled through the action of long stretches of noncoding DNA that contain enhancers-shorter sequences responsible for controlling a single aspect of a gene's expression pattern. Models built on thermodynamics have shown how enhancers interpret protein concentration in order to determine specific levels of gene expression, but the emergent regulatory logic of a complete regulatory locus shows qualitative and quantitative differences from isolated enhancers. Such differences may arise from steric competition limiting the quantity of DNA that can simultaneously influence the transcription machinery. We incorporated this competition into a mechanistic model of gene regulation, generated efficient algorithms for this computation, and applied it to the regulation of Drosophila even-skipped (eve). This model finds the location of enhancers and identifies which factors control the boundaries of eve expression. This model predicts a new enhancer that, when assayed in vivo, drives expression in a non-eve pattern. Incorporation of chromatin accessibility eliminates this inconsistency.
引用
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页数:26
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