Mapping the regulatory landscape of the human GHRL promoter through integrative in- silico approaches

Background: Ghrelin, encoded by the human GHRL gene, regulates appetite and gastrointestinal motility, yet its transcriptional regulation remains poorly defined. Methods: We performed an integrative in silico analysis of the human GHRL promoter to identify regulatory elements, assess evolutionary conservation, and integrate epigenetic features. Promoter sequences were retrieved from curated databases and analyzed using position weight matrices to predict transcription factor binding sites (TFBS) with normalized affinity ≥0.85. Conservation scores (phastCons, phyloP) and epigenomic profiles (H3K4me3, H3K27ac, DNase-seq, ATAC-seq) were integrated from public datasets. Results: The promoter exhibited a complex architecture combining canonical motifs (TATA-like box, initiator) and non-canonical elements (downstream promoter element, E-box), along with high-density TFBS for nuclear receptors and stress-responsive factors. Conserved regions overlapped with predicted motifs, and epigenetic analysis revealed enrichment of activating histone marks and chromatin accessibility, with variability across developmental stages. Functional enrichment highlighted pathways related to metabolic regulation, hormonal signaling, and cell differentiation. No classical CpG islands were detected, suggesting regulation primarily through histone modifications rather than DNA methylation. Conclusions: These findings provide a comprehensive view of the regulatory landscape of the GHRL promoter and offer a reproducible computational framework to guide experimental validation and translational studies in gastrointestinal and metabolic contexts.