{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328309/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Mus musculus"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328309"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Functional evolution, modification, and derivatization of mammalian developmental enhancers","description":"This dataset encompasses two complementary massively parallel reporter assay (MPRA) studies that together dissect the functional architecture and evolutionary dynamics of mammalian cis-regulatory elements (CREs) at nucleotide resolution, using five parietal endoderm enhancers as a model system. The first study maps the functional evolution of these enhancers by testing orthologous sequences from 480 extant and ancestrally reconstructed mammalian genomes (Zoonomia/Cactus). Using a model-driven reconstitution strategy guided by deep learning predictions of chromatin accessibility, we traced causal transcription factor binding site (TFBS) changes across lineages, revealing pervasive context-dependent epistasis and diverse modes of evolutionary divergence. Targeted enhancer editing further demonstrated a striking asymmetry: ablation of enhancer activity required as few as one to seven mutations, whereas activity enhancement was constrained by element-specific ceilings. The second study subjects the same five enhancers to intensive sequence perturbation, assaying over 35,000 variants organized into four classes: dense multi-size tiling, multi-hit saturation mutagenesis, model-guided compaction, and TFBS-anchored sequence derivatization including synthetic thripsis. This dissection revealed sharp non-additivity between fragment size and activity, a spectrum of mutational robustness, rare but consequential inter-TFBS epistasis, and a strong influence of background sequence on enhancer output independent of TFBS arrangement. Together, these datasets provide a comprehensive resource for understanding how enhancer sequences encode function, robustness, and evolvability across the mammalian phylogeny.","dates":{"publication":"2026/04/20"},"accession":"GSE328309","cross_references":{"GSM":["GSM9678486","GSM9678485","GSM9678484","GSM9678483","GSM9678489","GSM9678488","GSM9678487","GSM9682835","GSM9678482","GSM9678481","GSM9678491","GSM9678480","GSM9678490"],"GPL":["30172"],"GSE":["328309"],"taxon":["Mus musculus"]}}