Transposable elements are the primary source of novelty in primate gene regulation.
Transposable elements are the primary source of novelty in primate gene regulation.
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DOI：
10.1101/gr.218149.116
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发表时间：
2017-10
期刊：
影响因子：
7
通讯作者：
Brown CD
中科院分区：
文献类型：
--
作者：
Trizzino M;Park Y;Holsbach-Beltrame M;Aracena K;Mika K;Caliskan M;Perry GH;Lynch VJ;Brown CD
基因调控塑造了表型多样性的进化。我们研究了六种灵长类动物肝脏启动子和增强子的进化，使用ChIP-seq（H3 K27 ac和H3 K4 me 1）来分析顺式调节元件（克雷斯），并使用RNA-seq来表征相同个体中的基因表达。为了量化监管分歧，我们通过测试直接测量的直系同源序列的差异ChIP-seq读取深度来比较不同物种的CRE活性。我们发现，灵长类动物的调控格局在整个谱系中基本上是保守的，63%的测试人类肝脏克雷斯在不同物种中表现出相似的活性。保守的CRE功能与序列保守性、与编码基因的接近性、细胞类型特异性和转录因子结合相关。新进化的克雷斯富含免疫应答和神经发育功能。我们进一步证明，保守的克雷斯绑定主调节器，这表明，虽然克雷斯有助于物种适应环境，核心功能保持不变。新进化的克雷斯富含年轻的转座因子（TE），包括长末端重复序列（LTR）和SINE-VNTR-Alus（SVA），其显著影响基因表达。相反，只有16%的保守克雷斯重叠TE。我们测试的顺式调节活性的69 TE亚家族的荧光素酶报告分析，跨越所有主要的TE类，并表明，95.6%的测试TE可以作为转录激活因子或阻遏物。总之，我们证明了TE在灵长类动物基因调控中的关键作用，并通过非编码基因组说明了灵长类动物物种之间进化分歧的潜在机制。
Gene regulation shapes the evolution of phenotypic diversity. We investigated the evolution of liver promoters and enhancers in six primate species using ChIP-seq (H3K27ac and H3K4me1) to profile cis-regulatory elements (CREs) and using RNA-seq to characterize gene expression in the same individuals. To quantify regulatory divergence, we compared CRE activity across species by testing differential ChIP-seq read depths directly measured for orthologous sequences. We show that the primate regulatory landscape is largely conserved across the lineage, with 63% of the tested human liver CREs showing similar activity across species. Conserved CRE function is associated with sequence conservation, proximity to coding genes, cell-type specificity, and transcription factor binding. Newly evolved CREs are enriched in immune response and neurodevelopmental functions. We further demonstrate that conserved CREs bind master regulators, suggesting that while CREs contribute to species adaptation to the environment, core functions remain intact. Newly evolved CREs are enriched in young transposable elements (TEs), including Long-Terminal-Repeats (LTRs) and SINE-VNTR-Alus (SVAs), that significantly affect gene expression. Conversely, only 16% of conserved CREs overlap TEs. We tested the cis-regulatory activity of 69 TE subfamilies by luciferase reporter assays, spanning all major TE classes, and showed that 95.6% of tested TEs can function as either transcriptional activators or repressors. In conclusion, we demonstrated the critical role of TEs in primate gene regulation and illustrated potential mechanisms underlying evolutionary divergence among the primate species through the noncoding genome.
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影响因子：
7
作者：
del Rosario RC;Rayan NA;Prabhakar S
通讯作者：
Prabhakar S
影响因子：
4.5
作者：
Brown CD;Mangravite LM;Engelhardt BE
通讯作者：
Engelhardt BE
DOI：
10.1126/science.aad5497
发表时间：
2016-03-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chuong EB;Elde NC;Feschotte C
通讯作者：
Feschotte C
模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y