Locus-Specific Enrichment Analysis of 5-Hydroxymethylcytosine Reveals Novel Genes Associated with Breast Carcinogenesis
An imbalance in DNA methylation is a hallmark epigenetic alteration in cancer. The conversion of 5-methylcytosine (5-mC) to 5-hydroxymethyl cytosine (5-hmC), which causes the imbalance, results in aberrant gene expression. The precise functional role of 5-hydroxymethylcytosine in breast cancer remai...
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MDPI AG
2022-09-01
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| author | Deepa Ramasamy Arunagiri Kuha Deva Magendhra Rao Meenakumari Balaiah Arvinden Vittal Rangan Shirley Sundersingh Sridevi Veluswami Rajkumar Thangarajan Samson Mani |
| author_facet | Deepa Ramasamy Arunagiri Kuha Deva Magendhra Rao Meenakumari Balaiah Arvinden Vittal Rangan Shirley Sundersingh Sridevi Veluswami Rajkumar Thangarajan Samson Mani |
| author_sort | Deepa Ramasamy |
| collection | DOAJ |
| description | An imbalance in DNA methylation is a hallmark epigenetic alteration in cancer. The conversion of 5-methylcytosine (5-mC) to 5-hydroxymethyl cytosine (5-hmC), which causes the imbalance, results in aberrant gene expression. The precise functional role of 5-hydroxymethylcytosine in breast cancer remains elusive. In this study, we describe the landscape of 5-mC and 5-hmC and their association with breast cancer development. We found a distinguishable global loss of 5-hmC in the localized and invasive types of breast cancer that strongly correlate with <i>TET</i> expression. Genome-wide analysis revealed a unique 5-mC and 5-hmC signature in breast cancer. The differentially methylated regions (DMRs) were primarily concentrated in the proximal regulatory regions such as the promoters and UTRs, while the differentially hydroxymethylated regions (DhMRs) were densely packed in the distal regulatory regions, such as the intergenic regions (>−5 kb from TSSs). Our results indicate 4809 DMRs and 4841 DhMRs associated with breast cancer. Validation of nine 5-hmC enriched loci in a distinct set of breast cancer and normal samples positively correlated with their corresponding gene expression. The novel 5-hmC candidates such as TXNL1, and CNIH3 implicate a pro-oncogenic role in breast cancer. Overall, these results provide new insights into the loci-specific accumulation of 5-mC and 5-hmC, which are aberrantly methylated and demethylated in breast cancer. |
| first_indexed | 2024-03-09T21:55:06Z |
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| last_indexed | 2024-03-09T21:55:06Z |
| publishDate | 2022-09-01 |
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| series | Cells |
| spelling | doaj.art-c70f5a86e3654d72952abf064b92b16b2023-11-23T19:59:51ZengMDPI AGCells2073-44092022-09-011119293910.3390/cells11192939Locus-Specific Enrichment Analysis of 5-Hydroxymethylcytosine Reveals Novel Genes Associated with Breast CarcinogenesisDeepa Ramasamy0Arunagiri Kuha Deva Magendhra Rao1Meenakumari Balaiah2Arvinden Vittal Rangan3Shirley Sundersingh4Sridevi Veluswami5Rajkumar Thangarajan6Samson Mani7Department of Molecular Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai 600036, Tamilnadu, IndiaDepartment of Molecular Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai 600036, Tamilnadu, IndiaDepartment of Molecular Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai 600036, Tamilnadu, IndiaDepartment of Molecular Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai 600036, Tamilnadu, IndiaDepartment of Oncopathology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai 600036, Tamilnadu, IndiaDepartment of Surgical Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai 600036, Tamilnadu, IndiaDepartment of Molecular Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai 600036, Tamilnadu, IndiaDepartment of Molecular Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai 600036, Tamilnadu, IndiaAn imbalance in DNA methylation is a hallmark epigenetic alteration in cancer. The conversion of 5-methylcytosine (5-mC) to 5-hydroxymethyl cytosine (5-hmC), which causes the imbalance, results in aberrant gene expression. The precise functional role of 5-hydroxymethylcytosine in breast cancer remains elusive. In this study, we describe the landscape of 5-mC and 5-hmC and their association with breast cancer development. We found a distinguishable global loss of 5-hmC in the localized and invasive types of breast cancer that strongly correlate with <i>TET</i> expression. Genome-wide analysis revealed a unique 5-mC and 5-hmC signature in breast cancer. The differentially methylated regions (DMRs) were primarily concentrated in the proximal regulatory regions such as the promoters and UTRs, while the differentially hydroxymethylated regions (DhMRs) were densely packed in the distal regulatory regions, such as the intergenic regions (>−5 kb from TSSs). Our results indicate 4809 DMRs and 4841 DhMRs associated with breast cancer. Validation of nine 5-hmC enriched loci in a distinct set of breast cancer and normal samples positively correlated with their corresponding gene expression. The novel 5-hmC candidates such as TXNL1, and CNIH3 implicate a pro-oncogenic role in breast cancer. Overall, these results provide new insights into the loci-specific accumulation of 5-mC and 5-hmC, which are aberrantly methylated and demethylated in breast cancer.https://www.mdpi.com/2073-4409/11/19/2939DNA methylation or 5-methylcytosine5-hydroxymethyl cytosinemethylation imbalancebreast cancerDMRDhMR |
| spellingShingle | Deepa Ramasamy Arunagiri Kuha Deva Magendhra Rao Meenakumari Balaiah Arvinden Vittal Rangan Shirley Sundersingh Sridevi Veluswami Rajkumar Thangarajan Samson Mani Locus-Specific Enrichment Analysis of 5-Hydroxymethylcytosine Reveals Novel Genes Associated with Breast Carcinogenesis Cells DNA methylation or 5-methylcytosine 5-hydroxymethyl cytosine methylation imbalance breast cancer DMR DhMR |
| title | Locus-Specific Enrichment Analysis of 5-Hydroxymethylcytosine Reveals Novel Genes Associated with Breast Carcinogenesis |
| title_full | Locus-Specific Enrichment Analysis of 5-Hydroxymethylcytosine Reveals Novel Genes Associated with Breast Carcinogenesis |
| title_fullStr | Locus-Specific Enrichment Analysis of 5-Hydroxymethylcytosine Reveals Novel Genes Associated with Breast Carcinogenesis |
| title_full_unstemmed | Locus-Specific Enrichment Analysis of 5-Hydroxymethylcytosine Reveals Novel Genes Associated with Breast Carcinogenesis |
| title_short | Locus-Specific Enrichment Analysis of 5-Hydroxymethylcytosine Reveals Novel Genes Associated with Breast Carcinogenesis |
| title_sort | locus specific enrichment analysis of 5 hydroxymethylcytosine reveals novel genes associated with breast carcinogenesis |
| topic | DNA methylation or 5-methylcytosine 5-hydroxymethyl cytosine methylation imbalance breast cancer DMR DhMR |
| url | https://www.mdpi.com/2073-4409/11/19/2939 |
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