Identification of key tissue-specific, biological processes by integrating enhancer information in maize gene regulatory networks

Abstract

Enhancers are important regulators of gene expression during numerous crucial processes including tissue differentiation across development. In plants, their recent molecular characterization revealed their capacity to activate the expression of several target genes through the binding of transcription factors. Nevertheless, identifying these target genes at a genome-wide level remains a challenge, in particular in species with large genomes, where enhancers and target genes can be hundreds of kilobases away. Therefore, the contribution of enhancers to regulatory network is still poorly understood in plants. In this study, we investigate the enhancer-driven regulatory network of two maize tissues at different stages: leaves at seedling stage and husks (bracts) at flowering. Using a systems biology approach, we integrate genomic, epigenomic and transcriptomic data to model the regulatory relationship between transcription factors and their potential target genes. We identify regulatory modules specific to husk and V2-IST, and show that they are involved in distinct functions related to the biology of each tissue. We evidence enhancers exhibiting binding sites for two distinct transcription factor families (DOF and AP2/ERF) that drive the tissue-specificity of gene expression in seedling immature leaf and husk. Analysis of the corresponding enhancer sequences reveals that two different transposable element families (TIR transposon Mutator and MITE Pif/Harbinger ) have shaped the regulatory network in each tissue, and that MITEs have provided new transcription factor binding sites that are involved in husk tissue-specificity.

Identification of Key Tissue-Specific, Biological Processes by Integrating Enhancer Information in Maize Gene Regulatory Networks

“…We thank the Genotoul bioinformatics platform Toulouse Midi-Pyrenees for providing computing and storage resources, Shujun Ou for providing an upgraded TE maize database that we used for TE annotation, Anthony Mathelier for help with TFBS identification, and Megha Padi for assistance with ALPACA. This manuscript has been released as a pre-print at https://www.biorxiv.org/content/10.1101/2020.06.16.155481v1 , (Fagny et al, 2020 ).…”

A comprehensive map of preferentially located motifs reveals distinct proximal cis-regulatory sequences in plants

“…Numerous experimental and predictive efforts (Lai et al, 2019;Savadel et al, 2021;Schmitz et al, 2021) have been made to characterize them, highlighting several cisregulatory regions. In addition to the distal cis-regulatory DNA sequences, which include enhancers (Fagny et al, 2021) and can be more than 1 Mbp away from their target gene, there are the 5'-and 3'-gene-proximal regions that are rich in cis-regulatory DNA sequences (Li et al, 2012;Wallace et al, 2014;Zemlyanskaya et al, 2021).…”

Data_Sheet_1.pdf

“…This manuscript has been released as a pre-print at https://www.biorxiv.org/content/10. 1101/2020.06.16.155481v1, (Fagny et al, 2020).…”