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ORIGINAL RESEARCH article
Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1553469
This article is part of the Research Topic Comparative Genomics and Functional Genomics Analyses in Cancer View all 3 articles
Combined promoter-capture Hi-C and Hi-C analysis reveals a fine-tuned regulation of 3D chromatin architecture in colorectal cancer
Provisionally accepted- 1 Indian Institute of Science Education and Research, Pune, Pune, Maharashtra, India
- 2 Institute of Advanced Study in Science and Technology, Department of Science and Technology, Ministry of Science and Technology (India), Guwahati, Assam, India
- 3 Amity University Gurgaon, Gurgaon, Haryana, India
- 4 Shiv Nadar University, Greater Noida, Uttar Pradesh, India
Hi-C is a widely used method for profiling chromosomal interactions in the 3-dimensional context.Due to limitations on the depth of sequencing, the resolution of most Hi-C datasets is often insufficient for scoring fine-scale interactions. We therefore used promoter-capture Hi-C (PCHi-C) data for mapping these subtle interactions. From multiple colorectal cancer (CRC) studies, we combined PCHi-C with Hi-C datasets to understand the dynamics of chromosomal interactions from cis regulatory elements to topologically associated domain (TAD)-level, enabling detection of fine-scale interactions of disease-associated loci within TADs. Our integrated analyses of PCHi-C and Hi-C datasets from CRC cell lines along with histone modification landscape and transcriptome signatures highlight significant genomic structural instability and their association with tumor-suppressive transcriptional programs. Such analyses also yielded nine dysregulated genes. Transcript profiling revealed a dramatic increase in their expression in CRC cell lines as compared to NT2D1 human embryonic carcinoma cells, supporting the predictions of our bioinformatics analysis. We further report increased occupancy of activation associated histone modifications H3K27ac and H3K4me3 at the promoter regions of the targets analyzed. Our study provides deeper insights into the dynamic 3D genome organization in CRC and identification of affected genes which may serve as potential biomarkers for CRC.
Keywords: colorectal cancer, TADs, genome organization, epigenome, Gene Expression, biomarker
Received: 30 Dec 2024; Accepted: 24 Feb 2025.
Copyright: © 2025 Kumar, Madhok, BHattacharya, Nandi and Galande. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Soumyadeep Nandi, Amity University Gurgaon, Gurgaon, 122 413, Haryana, India
Sanjeev Galande, Shiv Nadar University, Greater Noida, Uttar Pradesh, India
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