Limited conservation in cross-species comparison of GLK transcription factor binding suggested wide-spread cistrome divergence

Authors: TU, XIAOYU - The Chinese University Of Hong Kong (CUHK); REN, SIBO - The Chinese University Of Hong Kong (CUHK); WEI, SEN - The Chinese University Of Hong Kong (CUHK); LI, JIANJIAN - The Chinese University Of Hong Kong (CUHK); LI, YUXIANG - The Chinese University Of Hong Kong (CUHK); LI, CHUANSHUN - Shanghai Jiaotong University; LI, YANGMEIHIU - Shanghai Jiaotong University; ZHONG, ZHANXIANG - Huazhong Agricultural University; XIE, WEIBO - Huazhong Agricultural University; GRIERSON, DONALD - Zheijiang University; FEI, ZHANGJUN - Boyce Thompson Institute; Giovannoni, James; LI, PINGHUA - Shandong Agricultural University; ZHONG, SILIN - The Chinese University Of Hong Kong (CUHK)

Submitted to: Nature Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/2/2022
Publication Date: 12/9/2022
Citation: Tu, X., Ren, S., Wei, S., Li, J., Li, Y., Li, C., Li, Y., Zhong, Z., Xie, W., Grierson, D., Fei, Z., Giovannoni, J.J., Li, P., Zhong, S. 2022. Limited conservation in cross-species comparison of GLK transcription factor binding suggested wide-spread cistrome divergence. Nature Communications. 13(1). Article 7632. https://doi.org/10.1038/s41467-022-35438-4.
DOI: https://doi.org/10.1038/s41467-022-35438-4

Interpretive Summary: Transcription factor (TF) binding to gene regulatory elements is crucial to gene regulation. The genome-wide map of all these regulatory interactions is often referred to as the cistrome. Its dynamics enabled species and individuals with similar genes to generate different transcriptional programs and, as a consequence, different phenotypes, and contributed greatly to species’ adaptation. In this study, we map the DNA binding sites in five representative plant species to a GLK transcription factors which regulate chloroplast development and thus photosynthetic capacity and and find that most of the GLK-bound genes are species-specific. The conserved GLK-bound genes are often associated with photosynthetic function as anticipated, and their expression changes in the presence of GLK mutation consistent with the regulatory rol of this protein on these genes. Our results reveal widespread genome (specifically cistrome) divergence in GLK interactions with different genes during plant evolution, indicating the importance of altered photosynthetic phenotypes in plant adaptation.

Technical Abstract: Non-coding cis-regulatory variants in animal genomes are an important driving force in the evolution of transcription regulation and phenotype diversity. However, cistrome dynamics in plants remain largely underexplored. Here, we compare the binding of GOLDEN2-LIKE (GLK) transcription factors in tomato, tobacco, Arabidopsis, maize and rice. Although the function of GLKs is conserved, most of their binding sites are species-specific. Conserved binding sites are often found near photosynthetic genes dependent on GLK for expression, but sites near non-differentially expressed genes in the glk mutant are nevertheless under purifying selection. The binding sites’ regulatory potential can be predicted by machine learning model using quantitative genome features and TF co-binding information. Our study show that genome cis-variation caused wide-spread TF binding divergence, and most of the TF binding sites are genetically redundant. This poses a major challenge for interpreting the effect of individual sites and highlights the importance of quantitatively measuring TF occupancy.