Integrative analyses of chromosome conformation, chromatin accessibility and gene expression in human and livestock genomes. As available “omics” data keep increasing in volume and heterogeneity, integrating sequencing datasets from various molecular assays has become a crucial challenge to investigate how genomes are organized and operate. Here we present several approaches to explore the links between genome structure and function by analyzing different types of sequencing data. In particular, we focus on gene expression, chromatin accessibility and chromosome conformation assays. First, using public data from the ENCODE project we show concrete examples of what can or cannot easily be done to investigate enhancer/gene interactions in the human genome by combining results from DNAse-seq, RNA-seq and (capture-)Hi-C or ChIA-PET. We present correlation-based strategies from published studies and comment on the issue of defining a reference dataset. Then, we use data that were generated in the context of the FAANG pilot project FR-AgENCODE, which aims at improving genome annotation in livestock species (cow, pig, goat and chicken). We show global consistency between genome structure and function. Notably, both RNA-seq and ATAC-seq normalized read counts are significantly higher in active “A” vs. inactive “B” Hi-C compartments. We also investigate the correlation between gene expression and promoter accessibility across samples, and how part of these results can be obtained in human with RNA-seq and DNAse-seq data from the Epigenome Roadmap project.