GCREs

GCREs, in genomics, commonly refers to genome-conserved regulatory elements. These are regulatory DNA sequences whose nucleotide sequences show conservation across multiple species, implying functional constraint. GCREs typically function as cis-regulatory elements such as promoters, enhancers, silencers, and insulators that help control gene expression in a tissue- or development-specific manner. While the term is not universally standardized, it is widely used to denote sequences identified through cross-species conservation and associated regulatory activity.

Identification and validation of GCREs rely on both computational and experimental approaches. Conservation-based methods (for example, phastCons, phyloP, and GERP++) highlight candidate elements by detecting lineage-restricted or widespread constraint. Experimental data from ATAC-seq or DNase-seq reveal accessible chromatin, and ChIP-seq for histone marks such as H3K27ac and H3K4me1 supports regulatory potential. Functional validation can employ reporter assays, massively parallel reporter assays (MPRA), or genome perturbation techniques like CRISPR-Cas9 to assess the impact on gene expression. Linking GCREs to target genes often uses chromatin interaction data (Hi-C, promoter capture Hi-C) and expression quantitative trait loci (eQTL) analyses.

Significance and limitations: GCREs aid in annotating regulatory landscapes, understanding the evolution of gene regulation, and interpreting noncoding genetic variation in disease. However, conservation does not guarantee function, and many regulatory elements are lineage-specific and not captured by cross-species conservation alone. In other fields, GCREs may have different meanings, so the intended interpretation depends on the disciplinary context.