Comprehensive analysis of H3K27me3 LOCKs under different DNA methylation contexts reveal epigenetic redistribution in tumorigenesis
Abstract Background Histone modification H3K27me3 plays a critical role in normal development and is associated with various diseases, including cancer. This modification forms large chromatin domains, known as Large Organized Chromatin Lysine Domains (LOCKs), which span several hundred kilobases. R...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Epigenetics & Chromatin |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13072-025-00570-0 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585345717239808 |
|---|---|
| author | Yuan Liang Mengni Liu Bingyuan Liu Benjamin Ziman Guanjie Peng Qiong Mao Xingzhe Wang Lizhen Jiang De-Chen Lin Yueyuan Zheng |
| author_facet | Yuan Liang Mengni Liu Bingyuan Liu Benjamin Ziman Guanjie Peng Qiong Mao Xingzhe Wang Lizhen Jiang De-Chen Lin Yueyuan Zheng |
| author_sort | Yuan Liang |
| collection | DOAJ |
| description | Abstract Background Histone modification H3K27me3 plays a critical role in normal development and is associated with various diseases, including cancer. This modification forms large chromatin domains, known as Large Organized Chromatin Lysine Domains (LOCKs), which span several hundred kilobases. Result In this study, we identify and categorize H3K27me3 LOCKs in 109 normal human samples, distinguishing between long and short LOCKs. Our findings reveal that long LOCKs are predominantly associated with developmental processes, while short LOCKs are enriched in poised promoters and are most associated with low gene expression. Further analysis of LOCKs in different DNA methylation contexts shows that long LOCKs are primarily located in partially methylated domains (PMDs), particularly in short-PMDs, where they are most likely responsible for the low expressions of oncogenes. We observe that in cancer cell lines, including those from esophageal and breast cancer, long LOCKs shift from short-PMDs to intermediate-PMDs and long-PMDs. Notably, a significant subset of tumor-associated long LOCKs in intermediate- and long-PMDs exhibit reduced H3K9me3 levels, suggesting that H3K27me3 compensates for the loss of H3K9me3 in tumors. Additionally, we find that genes upregulated in tumors following the loss of short LOCKs are typically poised promoter genes in normal cells, and their transcription is regulated by the ETS1 transcription factor. Conclusion These results provide new insights into the role of H3K27me3 LOCKs in cancer and underscore their potential impact on epigenetic regulation and disease mechanisms. |
| format | Article |
| id | doaj-art-38c9df4420bf43ba957318bf6c622a75 |
| institution | Kabale University |
| issn | 1756-8935 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj-art-38c9df4420bf43ba957318bf6c622a752025-01-26T12:53:02ZengBMCEpigenetics & Chromatin1756-89352025-01-0118112110.1186/s13072-025-00570-0Comprehensive analysis of H3K27me3 LOCKs under different DNA methylation contexts reveal epigenetic redistribution in tumorigenesisYuan Liang0Mengni Liu1Bingyuan Liu2Benjamin Ziman3Guanjie Peng4Qiong Mao5Xingzhe Wang6Lizhen Jiang7De-Chen Lin8Yueyuan Zheng9Clinical Big Data Research Center, Scientific Research Center, Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research, The Seventh Affiliated Hospital of Sun Yat-Sen UniversityClinical Big Data Research Center, Scientific Research Center, Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research, The Seventh Affiliated Hospital of Sun Yat-Sen UniversityClinical Big Data Research Center, Scientific Research Center, Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research, The Seventh Affiliated Hospital of Sun Yat-Sen UniversityCenter for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, and Norris Comprehensive Cancer Center, University of Southern CaliforniaClinical Big Data Research Center, Scientific Research Center, Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research, The Seventh Affiliated Hospital of Sun Yat-Sen UniversityClinical Big Data Research Center, Scientific Research Center, Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research, The Seventh Affiliated Hospital of Sun Yat-Sen UniversityClinical Big Data Research Center, Scientific Research Center, Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research, The Seventh Affiliated Hospital of Sun Yat-Sen UniversityClinical Big Data Research Center, Scientific Research Center, Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research, The Seventh Affiliated Hospital of Sun Yat-Sen UniversityCenter for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, and Norris Comprehensive Cancer Center, University of Southern CaliforniaClinical Big Data Research Center, Scientific Research Center, Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research, The Seventh Affiliated Hospital of Sun Yat-Sen UniversityAbstract Background Histone modification H3K27me3 plays a critical role in normal development and is associated with various diseases, including cancer. This modification forms large chromatin domains, known as Large Organized Chromatin Lysine Domains (LOCKs), which span several hundred kilobases. Result In this study, we identify and categorize H3K27me3 LOCKs in 109 normal human samples, distinguishing between long and short LOCKs. Our findings reveal that long LOCKs are predominantly associated with developmental processes, while short LOCKs are enriched in poised promoters and are most associated with low gene expression. Further analysis of LOCKs in different DNA methylation contexts shows that long LOCKs are primarily located in partially methylated domains (PMDs), particularly in short-PMDs, where they are most likely responsible for the low expressions of oncogenes. We observe that in cancer cell lines, including those from esophageal and breast cancer, long LOCKs shift from short-PMDs to intermediate-PMDs and long-PMDs. Notably, a significant subset of tumor-associated long LOCKs in intermediate- and long-PMDs exhibit reduced H3K9me3 levels, suggesting that H3K27me3 compensates for the loss of H3K9me3 in tumors. Additionally, we find that genes upregulated in tumors following the loss of short LOCKs are typically poised promoter genes in normal cells, and their transcription is regulated by the ETS1 transcription factor. Conclusion These results provide new insights into the role of H3K27me3 LOCKs in cancer and underscore their potential impact on epigenetic regulation and disease mechanisms.https://doi.org/10.1186/s13072-025-00570-0H3K27me3 modificationDNA methylationLarge organized chromatin lysine domainsPartially methylated domainsTumor |
| spellingShingle | Yuan Liang Mengni Liu Bingyuan Liu Benjamin Ziman Guanjie Peng Qiong Mao Xingzhe Wang Lizhen Jiang De-Chen Lin Yueyuan Zheng Comprehensive analysis of H3K27me3 LOCKs under different DNA methylation contexts reveal epigenetic redistribution in tumorigenesis Epigenetics & Chromatin H3K27me3 modification DNA methylation Large organized chromatin lysine domains Partially methylated domains Tumor |
| title | Comprehensive analysis of H3K27me3 LOCKs under different DNA methylation contexts reveal epigenetic redistribution in tumorigenesis |
| title_full | Comprehensive analysis of H3K27me3 LOCKs under different DNA methylation contexts reveal epigenetic redistribution in tumorigenesis |
| title_fullStr | Comprehensive analysis of H3K27me3 LOCKs under different DNA methylation contexts reveal epigenetic redistribution in tumorigenesis |
| title_full_unstemmed | Comprehensive analysis of H3K27me3 LOCKs under different DNA methylation contexts reveal epigenetic redistribution in tumorigenesis |
| title_short | Comprehensive analysis of H3K27me3 LOCKs under different DNA methylation contexts reveal epigenetic redistribution in tumorigenesis |
| title_sort | comprehensive analysis of h3k27me3 locks under different dna methylation contexts reveal epigenetic redistribution in tumorigenesis |
| topic | H3K27me3 modification DNA methylation Large organized chromatin lysine domains Partially methylated domains Tumor |
| url | https://doi.org/10.1186/s13072-025-00570-0 |
| work_keys_str_mv | AT yuanliang comprehensiveanalysisofh3k27me3locksunderdifferentdnamethylationcontextsrevealepigeneticredistributionintumorigenesis AT mengniliu comprehensiveanalysisofh3k27me3locksunderdifferentdnamethylationcontextsrevealepigeneticredistributionintumorigenesis AT bingyuanliu comprehensiveanalysisofh3k27me3locksunderdifferentdnamethylationcontextsrevealepigeneticredistributionintumorigenesis AT benjaminziman comprehensiveanalysisofh3k27me3locksunderdifferentdnamethylationcontextsrevealepigeneticredistributionintumorigenesis AT guanjiepeng comprehensiveanalysisofh3k27me3locksunderdifferentdnamethylationcontextsrevealepigeneticredistributionintumorigenesis AT qiongmao comprehensiveanalysisofh3k27me3locksunderdifferentdnamethylationcontextsrevealepigeneticredistributionintumorigenesis AT xingzhewang comprehensiveanalysisofh3k27me3locksunderdifferentdnamethylationcontextsrevealepigeneticredistributionintumorigenesis AT lizhenjiang comprehensiveanalysisofh3k27me3locksunderdifferentdnamethylationcontextsrevealepigeneticredistributionintumorigenesis AT dechenlin comprehensiveanalysisofh3k27me3locksunderdifferentdnamethylationcontextsrevealepigeneticredistributionintumorigenesis AT yueyuanzheng comprehensiveanalysisofh3k27me3locksunderdifferentdnamethylationcontextsrevealepigeneticredistributionintumorigenesis |