Regulome

Regulome refers to the complete set of regulatory components that govern gene expression in a cell or organism. It includes DNA sequences with regulatory function such as promoters, enhancers, silencers, and insulators; transcription factors and co-regulators; non-coding RNAs; and the epigenetic and chromatin features that influence accessibility and activity. The regulome also encompasses the three-dimensional organization of the genome and the regulatory interactions that connect distal elements to target genes, forming transcriptional networks that respond to developmental cues and environmental signals.

The regulome is highly context-dependent, varying across cell types, developmental stages, and physiological conditions. Mapping the regulome involves identifying regulatory elements, their states, and their target genes, and integrating genetic variation that modulates regulation. Large consortia such as ENCODE and the Roadmap Epigenomics Project have produced comprehensive maps using assays for chromatin accessibility (DNase-seq, ATAC-seq), histone modifications (ChIP-seq for H3K27ac, H3K4me1, etc.), transcription factor binding, and chromatin conformation (Hi-C, capture Hi-C). Experimental approaches include CRISPR-based screens to test regulatory function and expression quantitative trait locus (eQTL) analyses to link variants with gene expression.

Regulome-wide data are increasingly used to interpret genome-wide association study results by linking noncoding variants to regulatory elements and their target genes, improving functional annotation and understanding disease mechanisms. Challenges remain, including tissue-specificity, context-dependent regulatory activity, and the difficulty of assigning distal regulatory elements to their true target genes. The regulome thus provides an integrated view of gene regulation and its variation across biological contexts.