A cis-regulatory atlas in maize at single-cell resolution

A cis-regulatory atlas in maize at single-cell resolution
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DOI:
10.1016/j.cell.2021.04.014
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发表时间:
2021-05-27
期刊:
影响因子:
64.5
通讯作者:
Schmitz, Robert J.
Schmitz, Robert J.
中科院分区:
生物学1区
文献类型:
--
作者:
Marand, Alexandre P.;Chen, Zongliang;Schmitz, Robert J.

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顺式调控元件(CRE)编码时空基因表达程序的基因组蓝图,使细胞功能高度专业化。利用玉米6个器官的单细胞基因组学,我们通过绘制转录因子(TF)组合图谱,鉴定具有非细胞自主活性的转录因子,以及揭示高阶染色质相互作用的转录因子,确定了定义不同细胞特性和协调染色质组织的顺式和反式调节因子。在未甲基化的长末端重复反转录转座子中,细胞类型特异性CRE被富含增强子活性。此外,我们发现特定细胞类型的Cre是表型相关遗传变异的热点,并在现代玉米育种中成为选择的目标,突出了该Cre图谱的生物学意义。通过比较玉米和拟南芥的发育轨迹,我们发现TFS和Cres具有保守和发散的染色质动力学,显示了基因调控网络的广泛进化。除了这个丰富的数据集,我们还开发了单细胞分析软件苏格拉底,它可以用来理解任何物种中的顺式调控变异。
cis-regulatory elements (CREs) encode the genomic blueprints of spatiotemporal gene expression programs enabling highly specialized cell functions. Using single-cell genomics in six maize organs, we determined the cis- and trans-regulatory factors defining diverse cell identities and coordinating chromatin organization by profiling transcription factor (TF) combinatorics, identifying TFs with non-cell-autonomous activity, and uncovering TFs underlying higher-order chromatin interactions. Cell-type-specific CREs were enriched for enhancer activity and within unmethylated long terminal repeat retrotransposons. Moreover, we found cell-type-specific CREs are hotspots for phenotype-associated genetic variants and were targeted by selection during modern maize breeding, highlighting the biological implications of this CRE atlas. Through comparison of maize and Arabidopsis thaliana developmental trajectories, we identified TFs and CREs with conserved and divergent chromatin dynamics, showcasing extensive evolution of gene regulatory networks. In addition to this rich dataset, we developed single-cell analysis software, Socrates, which can be used to understand cis-regulatory variation in any species.