Catalytic domain-dependent and -independent transcriptional activities of the tumour suppressor histone H3K27 demethylase UTX/KDM6A in specific cancer types
The histone H3K27 demethylase, UTX/KDM6A, plays a critical role in the early development of vertebrates, and mutations are frequently found in various cancers. Several studies on developmental and cancer biology have focused on preferential transcriptional regulation by UTX independently of its H3K2...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2023.2222245 |
| _version_ | 1827811406292975616 |
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| author | Wendi Sun Kian Leong Lee Lorenz Poellinger Hisao Masai Hiroyuki Kato |
| author_facet | Wendi Sun Kian Leong Lee Lorenz Poellinger Hisao Masai Hiroyuki Kato |
| author_sort | Wendi Sun |
| collection | DOAJ |
| description | The histone H3K27 demethylase, UTX/KDM6A, plays a critical role in the early development of vertebrates, and mutations are frequently found in various cancers. Several studies on developmental and cancer biology have focused on preferential transcriptional regulation by UTX independently of its H3K27 demethylase catalytic activity. Here, we analysed gene expression profiles of wild-type (WT) UTX and a catalytic activity-defective mutant in 786-O and HCT116 cells and confirmed that catalytic activity-dependent and -independent regulation contributes to the expression of most of the target genes. Indeed, the catalytic activity-defective mutant suppressed colony formation similar to the WT in our assay system. However, the expression of several genes was significantly dependent on the catalytic activity of UTX in a cell type-specific manner, which could account for the inherent variation in the transcriptional landscape of various cancer types. The promoter/enhancer regions of the catalytic activity-dependent genes identified here were found to be preferentially modified with H3K4me1 and less with H3K27me3 than those of the independent genes. These findings, combined with previous reports, highlight not only the understanding of determinants for the catalytic activity dependency but also the development and application of pharmaceutical agents targeting the H3K27 or H3K4 modifications. |
| first_indexed | 2024-03-11T23:05:47Z |
| format | Article |
| id | doaj.art-ac19b9687676421585622fd8dc156a70 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:05:47Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-ac19b9687676421585622fd8dc156a702023-09-21T13:23:13ZengTaylor & Francis GroupEpigenetics1559-22941559-23082023-12-0118110.1080/15592294.2023.22222452222245Catalytic domain-dependent and -independent transcriptional activities of the tumour suppressor histone H3K27 demethylase UTX/KDM6A in specific cancer typesWendi Sun0Kian Leong Lee1Lorenz Poellinger2Hisao Masai3Hiroyuki Kato4National University of SingaporeNational University of SingaporeNational University of SingaporeTokyo Metropolitan Institute of Medical ScienceNational University of SingaporeThe histone H3K27 demethylase, UTX/KDM6A, plays a critical role in the early development of vertebrates, and mutations are frequently found in various cancers. Several studies on developmental and cancer biology have focused on preferential transcriptional regulation by UTX independently of its H3K27 demethylase catalytic activity. Here, we analysed gene expression profiles of wild-type (WT) UTX and a catalytic activity-defective mutant in 786-O and HCT116 cells and confirmed that catalytic activity-dependent and -independent regulation contributes to the expression of most of the target genes. Indeed, the catalytic activity-defective mutant suppressed colony formation similar to the WT in our assay system. However, the expression of several genes was significantly dependent on the catalytic activity of UTX in a cell type-specific manner, which could account for the inherent variation in the transcriptional landscape of various cancer types. The promoter/enhancer regions of the catalytic activity-dependent genes identified here were found to be preferentially modified with H3K4me1 and less with H3K27me3 than those of the independent genes. These findings, combined with previous reports, highlight not only the understanding of determinants for the catalytic activity dependency but also the development and application of pharmaceutical agents targeting the H3K27 or H3K4 modifications.http://dx.doi.org/10.1080/15592294.2023.2222245utxkdm6ah3k27 demethylaseepigeneticscatalytic activity dependencygene expression profilemllcancer |
| spellingShingle | Wendi Sun Kian Leong Lee Lorenz Poellinger Hisao Masai Hiroyuki Kato Catalytic domain-dependent and -independent transcriptional activities of the tumour suppressor histone H3K27 demethylase UTX/KDM6A in specific cancer types Epigenetics utx kdm6a h3k27 demethylase epigenetics catalytic activity dependency gene expression profile mll cancer |
| title | Catalytic domain-dependent and -independent transcriptional activities of the tumour suppressor histone H3K27 demethylase UTX/KDM6A in specific cancer types |
| title_full | Catalytic domain-dependent and -independent transcriptional activities of the tumour suppressor histone H3K27 demethylase UTX/KDM6A in specific cancer types |
| title_fullStr | Catalytic domain-dependent and -independent transcriptional activities of the tumour suppressor histone H3K27 demethylase UTX/KDM6A in specific cancer types |
| title_full_unstemmed | Catalytic domain-dependent and -independent transcriptional activities of the tumour suppressor histone H3K27 demethylase UTX/KDM6A in specific cancer types |
| title_short | Catalytic domain-dependent and -independent transcriptional activities of the tumour suppressor histone H3K27 demethylase UTX/KDM6A in specific cancer types |
| title_sort | catalytic domain dependent and independent transcriptional activities of the tumour suppressor histone h3k27 demethylase utx kdm6a in specific cancer types |
| topic | utx kdm6a h3k27 demethylase epigenetics catalytic activity dependency gene expression profile mll cancer |
| url | http://dx.doi.org/10.1080/15592294.2023.2222245 |
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