Dong Xiaowei, Haque Neshatul, Wagenknecht Jessica B, Zimmermann Michael T
Medical College of Wisconsin.
bioRxiv. 2025 Jul 10:2025.07.07.663564. doi: 10.1101/2025.07.07.663564.
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 modules in endocrine development remains unclear. We developed a computational pipeline to analyze bulk RNA-seq data from 54 human tissues and constructed tissue-specific co-expression networks for 30 core BAF complex genes. Weighted gene co-expression network analysis (WGCNA) and Louvain clustering identified gene modules for each tissue, which we compared to 46 curated BAF subcomplex gene sets using Jaccard similarity. In metabolically active non-endocrine tissues (kidney, skeletal muscle, vasculature, fibroblasts), we observed strong co-expression with canonical BAF (cBAF) and polybromo-associated BAF (pBAF) modules. Central nervous system tissues were dominated by neuron-specific BAF (nBAF) modules. Endocrine tissues (e.g., thyroid, adrenal) and gastrointestinal epithelia displayed co-expression profiles resembling smooth muscle-like BAF and pBAF modules, 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 tissue-specific gene expression profiling can 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 disease and provides a framework for identifying tissue-specific chromatin remodeling strategies.
BRG1/BRM相关因子(BAF)染色质重塑复合物对于正常内分泌功能至关重要,并与各种代谢和发育障碍有关。然而,内分泌发育中基于染色质的调控模块的全貌仍不清楚。我们开发了一种计算流程来分析来自54种人体组织的批量RNA测序数据,并为30个核心BAF复合物基因构建了组织特异性共表达网络。加权基因共表达网络分析(WGCNA)和Louvain聚类确定了每个组织的基因模块,我们使用Jaccard相似性将其与46个精心策划的BAF亚复合物基因集进行了比较。在代谢活跃的非内分泌组织(肾脏、骨骼肌、血管、成纤维细胞)中,我们观察到与典型BAF(cBAF)和多溴相关BAF(pBAF)模块有强烈的共表达。中枢神经系统组织以神经元特异性BAF(nBAF)模块为主。内分泌组织(如甲状腺、肾上腺)和胃肠道上皮显示出类似于平滑肌样BAF和pBAF模块的共表达谱,表明将激素分泌与收缩和屏障功能整合在一起的染色质程序。这些模式表明,每个组织都表现出BAF亚复合物的独特、非随机组合,可能反映了其功能性染色质状态。我们的结果表明,组织特异性基因表达谱可以揭示蛋白质复合物调控的差异。BAF染色质重塑复合物的模块化部署似乎是根据每个器官的功能需求量身定制的。这项研究为进一步研究内分泌发育和疾病中的表观遗传调控奠定了基础,并为识别组织特异性染色质重塑策略提供了框架。
Cochrane Database Syst Rev. 2018-1-22
2025-1
Cochrane Database Syst Rev. 2025-2-19
J Cancer Res Clin Oncol. 2021-7
Stem Cells Int. 2021-1-16
Epigenetics Chromatin. 2019-3-21
Nucleic Acids Res. 2019-1-8
Cell Metab. 2016-6-23
Database (Oxford). 2015-7-7
Nature. 2015-2-19
Nucleic Acids Res. 2015-1
Nat Genet. 2013-6