Deciphering Cancer-Specific H3K27ac Landscapes Through Systematic Multi-Omics Integration and Development of Open-Access Genomic Annotation Platform
- 1Inner Mongolia Key Laboratory of Biophysics and Bioinformatics, School of Physical Science and Technology, Inner Mongolia University, Hohhot 010021, China
- 2Inner Mongolia Traditional Chinese & Mongolian Medical Research Institute, Hohhot 010020, China
- 3School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China
Abstract
H3K27ac epigenetically modulates gene expression and serves as an indicator of cancer status. Although aberrant H3K27ac has been widely studied, a comprehensive landscape of cancer-specific H3K27ac patterns remains lacking. By integrating 209 H3K27ac ChIP-seq datasets across 48 tissues and cell types, we defined 3612 universally conserved regions and a vast repertoire of cancer-specific H3K27ac alterations. Strikingly, while cancer-specific H3K27ac gains were pervasive across leukemia, hepatocellular carcinoma, breast cancer, lung adenocarcinoma, and lymphoma, losses were remarkably rare. These cancer-specific H3K27ac gains were predominantly enriched in non-coding regions, where they were associated with increased chromatin accessibility and chromatin interactions, enabling the recruitment of oncogenic transcription factors to activate target genes. Conversely, cancer-specific H3K27ac losses preferentially occurred in promoters and correlated with chromatin compaction and transcriptional repression. Mechanistic multi-omics analyses in leukemia further demonstrated this epigenetic-structural coupling. Leukemia-specific H3K27ac gains established a permissive chromatin environment that facilitated oncogenic GATA1 binding and activation of its target gene TAL1. Within this context, TAL1 exhibited increased interaction with STIL, a well-known fusion partner implicated in leukemogenesis. To enable broader application of these findings, we developed an open-access web server for genomic annotation. Collectively, our study provides a comprehensive landscape of cancer-specific H3K27ac modifications, defining them as a functional epigenetic signature of oncogenic chromatin remodeling and offering an annotation resource for understanding the regulation of the cancer genome.
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BibTeX
@article{zhuang2026deciphering,
title = {{Deciphering Cancer-Specific H3K27ac Landscapes Through Systematic Multi-Omics Integration and Development of Open-Access Genomic Annotation Platform}},
author = {Yu-Shuo Zhuang and Yuan-Yuan Gao and Zhao-Yue Zhang and Zhe-Peng Wang and Jun-Jie Liu and Li-Rong Zhang and Siqin Bateer and Lu-Qiang Zhang},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219606},
url = {https://www.mdpi.com/1422-0067/27/21/9606},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Deciphering Cancer-Specific H3K27ac Landscapes Through Systematic Multi-Omics Integration and Development of Open-Access Genomic Annotation Platform
AU - Yu-Shuo Zhuang
AU - Yuan-Yuan Gao
AU - Zhao-Yue Zhang
AU - Zhe-Peng Wang
AU - Jun-Jie Liu
AU - Li-Rong Zhang
AU - Siqin Bateer
AU - Lu-Qiang Zhang
PY - 2026
DA - 2026/10/27
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219606
UR - https://www.mdpi.com/1422-0067/27/21/9606
AB - H3K27ac epigenetically modulates gene expression and serves as an indicator of cancer status. Although aberrant H3K27ac has been widely studied, a comprehensive landscape of cancer-specific H3K27ac patterns remains lacking. By integrating 209 H3K27ac ChIP-seq datasets across 48 tissues and cell types, we defined 3612 universally conserved regions and a vast repertoire of cancer-specific H3K27ac alterations. Strikingly, while cancer-specific H3K27ac gains were pervasive across leukemia, hepatocellular carcinoma, breast cancer, lung adenocarcinoma, and lymphoma, losses were remarkably rare. These cancer-specific H3K27ac gains were predominantly enriched in non-coding regions, where they were associated with increased chromatin accessibility and chromatin interactions, enabling the recruitment of oncogenic transcription factors to activate target genes. Conversely, cancer-specific H3K27ac losses preferentially occurred in promoters and correlated with chromatin compaction and transcriptional repression. Mechanistic multi-omics analyses in leukemia further demonstrated this epigenetic-structural coupling. Leukemia-specific H3K27ac gains established a permissive chromatin environment that facilitated oncogenic GATA1 binding and activation of its target gene TAL1. Within this context, TAL1 exhibited increased interaction with STIL, a well-known fusion partner implicated in leukemogenesis. To enable broader application of these findings, we developed an open-access web server for genomic annotation. Collectively, our study provides a comprehensive landscape of cancer-specific H3K27ac modifications, defining them as a functional epigenetic signature of oncogenic chromatin remodeling and offering an annotation resource for understanding the regulation of the cancer genome.
SN - 1422-0067
ER -