# Multi-Omics Analysis of the Co-Expression Features of Specific Neighboring Gene Pairs Suggests an Association with Catechin Regulation in Camellia sinensis

## TL;DR

This study explores how neighboring genes in tea plants are co-expressed and how this relates to catechin regulation, offering new insights into tea plant metabolism.

## Contribution

The study introduces a multi-omics approach to uncover regulatory features of neighboring gene pairs and their link to catechin metabolism in Camellia sinensis.

## Key findings

- Intergenic distance negatively correlates with co-expression strength, while gene length positively correlates.
- ATAC-seq and H3K27ac peaks are linked to higher expression levels in co-expressed gene pairs.
- Certain gene pairs show strong associations with catechin accumulation, particularly EGC and EGCG.

## Abstract

Background/Objectives: The arrangement and positioning of genes on chromosomes are non-random in plant genomes. Adjacent gene pairs often exhibit similar co-expression patterns and regulatory mechanisms. However, the genomic and epigenetic features influencing such co-expression, particularly in perennial crops like tea (Camellia sinensis), remain largely uncharacterized. Methods: Firstly, we identified 771 specific neighboring gene pairs (SNGs) in C. sinensis (YK10) and investigated the contributions of intergenic distance and gene length to SNGs’ co-expression. Secondly, we integrated multi-omics data including transcriptome, ATAC-seq, Hi-C and histone modification data to explore the factors influencing their co-expression. Thirdly, we employed logistic regression models to individually assess the contributions of nine factors—ATAC-seq, H3K27ac, Hi-C, GO, distance, length, promoter, enhancer, and expression level—to the co-expression of SNGs. Finally, by integrating co-expression networks with metabolic profiles, several transcription factors potentially involved in the regulation of catechin metabolic pathways were identified. Results: Intergenic distance was significantly negatively correlated with co-expression strength, while gene length showed a positive correlation. Furthermore, these two features exerted synergistic effects with threshold characteristics and functional significance. SNGs marked by either ATAC-seq or H3K27ac peaks displayed significantly higher expression levels, suggesting that epigenetic regulation promotes co-expression. In addition, correlation analysis revealed that the expression of certain SNGs was closely associated with catechin accumulation, particularly epicatechin gallate (EGC) and epigallocatechin gallate (EGCG), highlighting their potential role in modulating tissue-specific catechin levels. Conclusions: Collectively, this study reveals a multilayered regulatory framework governing SNG co-expression and provides theoretical insights and candidate regulators for understanding metabolic regulation in tea plants.