The genetic architecture of cell-type-specific cis-regulation

Alexandre P. Marand, Luguang Jiang, Fabio A Gomez-Cano, Mark A.A. Minow, Xuan Zhang, John Pablo Mendieta, Ziliang Luo, Sohyun Bang, Haidong Yan, Cullan Meyer, Luca Schlegel, Frank Johannes, Robert J. Schmitz
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Abstract

Gene expression and complex phenotypes are determined by the activity of cis-regulatory elements. However, an understanding of how extant genetic variants affect cis-regulatory activity remains limited. Here, we investigated the consequences of cis-regulatory diversity using single-cell genomics of >0.7 million nuclei across 172 maize inbreds. Our analyses pinpointed cis-regulatory elements distinct to domesticated maize and how transposons rewired the regulatory landscape. We found widespread chromatin accessibility variation associated with >4.6 million genetic variants with largely cell-type-specific effects. Variants in TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR binding sites were the most prevalent determinants of chromatin accessibility. Finally, integration of genetic variants associated with chromatin accessibility, organismal trait variation, and population differentiation revealed how local adaptation has rewired regulatory networks in unique cellular context to alter maize flowering phenotypes.
细胞类型特异性顺式调控的基因结构
基因表达和复杂表型是由顺式调节元件的活性决定的。然而,人们对现存遗传变异如何影响顺式调控活性的了解仍然有限。在这里,我们利用对 172 个玉米近交系中 70 万个细胞核的单细胞基因组学研究了顺式调控多样性的后果。我们的分析确定了与驯化玉米不同的顺式调控元件,以及转座子是如何重新连接调控景观的。我们发现广泛的染色质可及性变异与 460 万个遗传变异有关,这些变异在很大程度上具有细胞类型特异性效应。TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR结合位点的变异是染色质可及性最普遍的决定因素。最后,整合与染色质可及性、生物体性状变异和种群分化相关的基因变异,揭示了局部适应如何在独特的细胞环境中重新构建调控网络,从而改变玉米开花表型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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