Department of Plant Biology, Carnegie Institution for Science, 260 Panama Street, Stanford, CA, 94305, USA.
Heinrich-Heine University, Universitätsstraße 1, Düsseldorf, NRW, 40225, Germany.
Genome Biol. 2023 May 8;24(1):108. doi: 10.1186/s13059-023-02909-w.
Genetic variation in regulatory sequences that alter transcription factor (TF) binding is a major cause of phenotypic diversity. Brassinosteroid is a growth hormone that has major effects on plant phenotypes. Genetic variation in brassinosteroid-responsive cis-elements likely contributes to trait variation. Pinpointing such regulatory variations and quantitative genomic analysis of the variation in TF-target binding, however, remains challenging. How variation in transcriptional targets of signaling pathways such as the brassinosteroid pathway contributes to phenotypic variation is an important question to be investigated with innovative approaches.
Here, we use a hybrid allele-specific chromatin binding sequencing (HASCh-seq) approach and identify variations in target binding of the brassinosteroid-responsive TF ZmBZR1 in maize. HASCh-seq in the B73xMo17 F1s identifies thousands of target genes of ZmBZR1. Allele-specific ZmBZR1 binding (ASB) has been observed for 18.3% of target genes and is enriched in promoter and enhancer regions. About a quarter of the ASB sites correlate with sequence variation in BZR1-binding motifs and another quarter correlate with haplotype-specific DNA methylation, suggesting that both genetic and epigenetic variations contribute to the high level of variation in ZmBZR1 occupancy. Comparison with GWAS data shows linkage of hundreds of ASB loci to important yield and disease-related traits.
Our study provides a robust method for analyzing genome-wide variations of TF occupancy and identifies genetic and epigenetic variations of the brassinosteroid response transcription network in maize.
改变转录因子（TF）结合的调控序列中的遗传变异是表型多样性的主要原因。油菜素内酯是一种生长激素，对植物表型有重大影响。油菜素内酯反应顺式元件的遗传变异可能导致性状变异。然而，精确定位这种调节变化以及 TF-靶标结合的定量基因组分析仍然具有挑战性。油菜素内酯途径等信号通路的转录靶标变异如何导致表型变异，这是一个需要用创新方法进行研究的重要问题。
在这里，我们使用杂交等位基因特异性染色质结合测序（HASCh-seq）方法，鉴定了玉米中油菜素内酯反应 TF ZmBZR1 的靶标结合的变异。B73xMo17 F1s 的 HASCh-seq 鉴定了 ZmBZR1 的数千个靶基因。ZmBZR1 的等位基因特异性结合（ASB）在 18.3%的靶基因中观察到，并在启动子和增强子区域富集。大约四分之一的 ASB 位点与 BZR1 结合基序的序列变异相关，另有四分之一与单倍型特异性 DNA 甲基化相关，这表明遗传和表观遗传变异都有助于 ZmBZR1 占据的高度变异。与 GWAS 数据的比较表明，数百个 ASB 位点与重要的产量和疾病相关性状相关联。
我们的研究提供了一种分析 TF 占据的全基因组变异的稳健方法，并鉴定了玉米中油菜素内酯反应转录网络的遗传和表观遗传变异。
