Marand Alexandre P, Chen Zongliang, Gallavotti Andrea, Schmitz Robert J
Department of Genetics, University of Georgia, Athens, GA 30602, USA.
Waksman Institute, Rutgers University, Piscataway, NJ 08854, USA.
Cell. 2021 May 27;184(11):3041-3055.e21. doi: 10.1016/j.cell.2021.04.014. Epub 2021 May 7.
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.
顺式调控元件（CRE）编码时空基因表达程序的基因组蓝图，从而实现高度专业化的细胞功能。通过对六个玉米器官进行单细胞基因组学研究，我们确定了定义不同细胞身份并协调染色质组织的顺式和反式调控因子，方法包括分析转录因子（TF）组合、鉴定具有非细胞自主活性的TF以及揭示高阶染色质相互作用背后的TF。细胞类型特异性CRE富含增强子活性，并存在于未甲基化的长末端重复逆转座子中。此外，我们发现细胞类型特异性CRE是与表型相关的遗传变异的热点，并且在现代玉米育种过程中受到选择的靶向作用，这突出了这个CRE图谱的生物学意义。通过比较玉米和拟南芥的发育轨迹，我们鉴定了具有保守和不同染色质动态的TF和CRE，展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Socrates，可用于了解任何物种的顺式调控变异。
