Complexity and conservation of regulatory landscapes underlie evolutionary resilience of mammalian gene expression.
Complexity and conservation of regulatory landscapes underlie evolutionary resilience of mammalian gene expression.
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DOI：
10.1038/s41559-017-0377-2
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发表时间：
2018-01
影响因子：
16.8
通讯作者：
Flicek P
中科院分区：
文献类型：
--
作者：
Berthelot C;Villar D;Horvath JE;Odom DT;Flicek P
为了深入了解哺乳动物基因表达是如何通过快速进化的调控元件来控制的，我们联合分析了来自15个物种的肝脏样本中的启动子和增强子活性以及下游转录水平。与复杂的调控景观相关的基因通常表现出高表达水平，保持进化稳定。虽然调控元件的数量是转录输出和恢复力的关键驱动因素，但调控保守性很重要：在哺乳动物中活跃的元件最有效地稳定基因表达。相比之下，最近进化的增强子通常贡献较弱，与其高进化可塑性一致。在整个哺乳动物进化枝中观察到这些效应，并且对潜在的混杂因素（如基因表达水平）具有鲁棒性。以肝脏为代表的体细胞组织，我们的研究结果阐明了基因表达的进化稳定性如何与周围启动子和增强子的数量和保守性密切相关。
To gain insight into how mammalian gene expression is controlled by rapidly evolving regulatory elements, we jointly analysed promoter and enhancer activity with downstream transcription levels in liver samples from fifteen species. Genes associated with complex regulatory landscapes generally exhibit high expression levels that remain evolutionarily stable. While the number of regulatory elements is the key driver of transcriptional output and resilience, regulatory conservation matters: elements active across mammals most effectively stabilise gene expression. In contrast, recently-evolved enhancers typically contribute weakly, consistent with their high evolutionary plasticity. These effects are observed across the entire mammalian clade and robust to potential confounders, such as gene expression level. Using liver as a representative somatic tissue, our results illuminate how the evolutionary stability of gene expression is profoundly entwined with both the number and conservation of surrounding promoters and enhancers.
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影响因子：
4.5
作者：
Kutter C;Watt S;Stefflova K;Wilson MD;Goncalves A;Ponting CP;Odom DT;Marques AC
通讯作者：
Marques AC
影响因子：
14.9
作者：
Flicek P;Ahmed I;Amode MR;Barrell D;Beal K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fairley S;Fitzgerald S;Gil L;García-Girón C;Gordon L;Hourlier T;Hunt S;Juettemann T;Kähäri AK;Keenan S;Komorowska M;Kulesha E;Longden I;Maurel T;McLaren WM;Muffato M;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ritchie GR;Ruffier M;Schuster M;Sheppard D;Sobral D;Taylor K;Thormann A;Trevanion S;White S;Wilder SP;Aken BL;Birney E;Cunningham F;Dunham I;Harrow J;Herrero J;Hubbard TJ;Johnson N;Kinsella R;Parker A;Spudich G;Yates A;Zadissa A;Searle SM
通讯作者：
Searle SM
影响因子：
30.8
作者：
Kunarso, Galih;Chia, Na-Yu;Bourque, Guillaume
通讯作者：
Bourque, Guillaume
DOI：
10.4049/jimmunol.1502009
发表时间：
2016-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jubb AW;Young RS;Hume DA;Bickmore WA
通讯作者：
Bickmore WA
影响因子：
4
作者：
Arnosti, DN;Kulkarni, MM
通讯作者：
Kulkarni, MM