ArticleClinical and translational medicine2024
Three-dimensional chromatin landscapes in somatotroph tumour.
Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Integrating Hi-C data and RNA-seq data to reveal the 3D genome in sheep.BMC genomics · 2025Article
- Three-dimensional chromatin landscapes in somatotroph tumour.Clinical and translational medicine · 2024Article
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8 authors.
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Abstract
backgroundThe three-dimensional (3D) genome architecture plays a critical role inregulating gene expression. However, the specific alterations in thisarchitecture within somatotroph tumors and their implications for gene expression remain largely unexplored.
methodsWe employed Hi-C and RNA-seq analyses to compare the 3D genomic structures of somatotroph tumors with normal pituitary tissue. This comprehensive approachenabled the characterization of A/B compartments, topologically associateddomains (TADs), and chromatin loops, integrating these with gene expression patterns.
resultsWe observed a decrease in both the frequency of chromosomal interactions andthe size of TADs in tumor tissue compared to normal tissue. Conversely, the number of TADs and chromatin loops was found to be increased in tumors. Integrated analysis of Hi-C and RNA-seq data demonstrated that changes inhigher-order chromat in structure were associated with alterations in gene expression. Specifically, genes in A compartments showed higher density and increased expression relative to those in B compartments. Moreover, the weakand enhanced insulation boundaries were identified, and the associated genes were enriched in the Wnt/β-Catenin signaling pathway. We identified the gainedand lost loops in tumor and integrated these differences with transcriptional changes to examine the functional relevance of the identified loops. Notably, we observed an enhanced insulation boundary and a greater number of loops in the TCF7L2 gene region within tumors, which was accompanied by an upregulation of TCF7L2 expression. Subsequently, TCF7L2 expression was confirmed through qRT-PCR, and upregulated TCF7L2 prompted cell proliferation and growth hormone (GH) secretion in vitro.
conclusionOur results provide comprehensive 3D chromatin architecture maps of somatotroph tumors and offer a valuable resource for furthering the understanding of the underlying biology and mechanisms of gene expression regulation.
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