<p>Gene expression patterns are governed by the hierarchical organization of the genome. Numerous efforts, leveraging both polymer physics-based models and experimental imaging technologies, have sought to elucidate the structure-function relationship of chromatin fibers. However, a major challenge is posed by the multi-scale nature of chromatin organization. Here, we present an experimentally informed, polymer physics-based model capable of reconstructing chromatin structural ensembles by integrating low-resolution contact data with MNase-derived nucleosome positioning information. We apply our approach to multiple human genomic loci. Our analysis shows distinct structural features associated with active and inactive chromatin states, providing insights into the relationship between genomic organization and transcriptional activity. These findings offer a framework for understanding genome structure-function relationships.</p>