Tissue-specific co-expression patterns of BAF complex genes across human endocrine and non-endocrine tissues.

Abstract: BRG1/BRM-associated factor (BAF) chromatin remodeling complexes are essential for normal endocrine function and are implicated in various metabolic and developmental disorders. However, the full range of chromatin-based regulatory programs and their molecular configurations in endocrine development remains unclear. In this study, we developed a computational pipeline to analyze bulk RNA-seq data from 45 human tissues and constructed tissue-specific co-expression networks for 30 core BAF complex genes. Using co-expression network analysis and Louvain clustering, we identified co-expression patterns that formed coherent gene communities for each tissue, comprising different combinations of 46 curated BAF subcomplex genes. In metabolically active non-endocrine tissues (kidney, skeletal muscle, vasculature, and fibroblasts), we observed strong co-expression with canonical BAF (cBAF) and polybromo-associated BAF (pBAF) gene communities. Central nervous system tissues were dominated by the neuron-specific BAF (nBAF) complex. Endocrine tissues (e.g., thyroid, adrenal) and gastrointestinal epithelia displayed co-expression profiles resembling smooth muscle-such as BAF and pBAF complexes, suggesting chromatin programs that integrate hormone secretion with contractile and barrier functions. These patterns show that each tissue exhibits a distinct, non-random combination of BAF subcomplexes, potentially reflecting its functional chromatin state. Our results demonstrate that latent patterns in tissue-specific gene expression profiles may reveal differences in protein complex regulation. The modular deployment of BAF chromatin remodeling complexes appears tailored to the functional demands of each organ. This study lays a foundation for further investigation of epigenetic regulation in endocrine development and pathobiological mechanisms and provides a framework for identifying tissue-specific chromatin remodeling strategies. Plain language summary: The US National Institutes of Health has invested in large-scale measurements of how different human body tissues use their genetic material. The current study leverages per-tissue genomics data to better understand how various genes come together to form protein complexes, analogous to nanomachines, that in turn regulate the same genetic material. As the first research of its type, we focused on one category of protein complex, namely BAF, to develop the statistical approach needed.