Chromatin state origins of uterine leiomyoma
Abstract Aberrations in the regulatory genome play a pivotal role in population-level disease predisposition. Annotation of the regulatory regions using appropriate primary tissues - instead of cell lines affected by selection and other confounding factors - could shed new light into mechanisms unde...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59646-w |
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| author | Maritta Räisänen Eevi Kaasinen Maija Jäntti Aurora Taira Emma Siili Ralf Bützow Oskari Heikinheimo Annukka Pasanen Auli Karhu FinnGen Davide G. Berta Niko Välimäki Lauri A. Aaltonen |
| author_facet | Maritta Räisänen Eevi Kaasinen Maija Jäntti Aurora Taira Emma Siili Ralf Bützow Oskari Heikinheimo Annukka Pasanen Auli Karhu FinnGen Davide G. Berta Niko Välimäki Lauri A. Aaltonen |
| author_sort | Maritta Räisänen |
| collection | DOAJ |
| description | Abstract Aberrations in the regulatory genome play a pivotal role in population-level disease predisposition. Annotation of the regulatory regions using appropriate primary tissues - instead of cell lines affected by selection and other confounding factors - could shed new light into mechanisms underlying common conditions. We test this approach in uterine leiomyomas, highly prevalent benign neoplasms of the myometrium, by creating 15-state chromatin annotations for myometrium and uterine leiomyomas. Integration with RNA-seq, ATAC-seq, HiChIP and methylation data enables us to compare the epigenomes of myometrium and ULs with distinct driver mutations, highlighting the role of bivalent regions in the neoplastic process. Subsequently, a genome wide association study meta-analysis is performed, using three different cohorts. Disease association loci are enriched at active chromatin, especially at enhancers, and harbor tumor- and driver mutation-specific chromatin states. At SATB2 locus we show the effect of the risk genotype already in the normal tissue. Integration of genome-wide association studies and deep regulatory genomics data from the correct tissue type represents a powerful approach in understanding population-level disease predisposition. |
| format | Article |
| id | doaj-art-c6ba4dfd48df4232904568a78b29b191 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-c6ba4dfd48df4232904568a78b29b1912025-08-20T03:53:12ZengNature PortfolioNature Communications2041-17232025-05-0116111610.1038/s41467-025-59646-wChromatin state origins of uterine leiomyomaMaritta Räisänen0Eevi Kaasinen1Maija Jäntti2Aurora Taira3Emma Siili4Ralf Bützow5Oskari Heikinheimo6Annukka Pasanen7Auli Karhu8FinnGenDavide G. Berta9Niko Välimäki10Lauri A. Aaltonen11Department of Medical and Clinical Genetics, University of HelsinkiDepartment of Medical and Clinical Genetics, University of HelsinkiDepartment of Medical and Clinical Genetics, University of HelsinkiDepartment of Medical and Clinical Genetics, University of HelsinkiDepartment of Pathology, University of Helsinki and Helsinki University HospitalApplied Tumor Genomics Research Program, Research Programs Unit, University of HelsinkiDepartment of Obstetrics and Gynecology, University of Helsinki and Helsinki University HospitalDepartment of Pathology, University of Helsinki and Helsinki University HospitalDepartment of Medical and Clinical Genetics, University of HelsinkiDepartment of Medical and Clinical Genetics, University of HelsinkiDepartment of Medical and Clinical Genetics, University of HelsinkiDepartment of Medical and Clinical Genetics, University of HelsinkiAbstract Aberrations in the regulatory genome play a pivotal role in population-level disease predisposition. Annotation of the regulatory regions using appropriate primary tissues - instead of cell lines affected by selection and other confounding factors - could shed new light into mechanisms underlying common conditions. We test this approach in uterine leiomyomas, highly prevalent benign neoplasms of the myometrium, by creating 15-state chromatin annotations for myometrium and uterine leiomyomas. Integration with RNA-seq, ATAC-seq, HiChIP and methylation data enables us to compare the epigenomes of myometrium and ULs with distinct driver mutations, highlighting the role of bivalent regions in the neoplastic process. Subsequently, a genome wide association study meta-analysis is performed, using three different cohorts. Disease association loci are enriched at active chromatin, especially at enhancers, and harbor tumor- and driver mutation-specific chromatin states. At SATB2 locus we show the effect of the risk genotype already in the normal tissue. Integration of genome-wide association studies and deep regulatory genomics data from the correct tissue type represents a powerful approach in understanding population-level disease predisposition.https://doi.org/10.1038/s41467-025-59646-w |
| spellingShingle | Maritta Räisänen Eevi Kaasinen Maija Jäntti Aurora Taira Emma Siili Ralf Bützow Oskari Heikinheimo Annukka Pasanen Auli Karhu FinnGen Davide G. Berta Niko Välimäki Lauri A. Aaltonen Chromatin state origins of uterine leiomyoma Nature Communications |
| title | Chromatin state origins of uterine leiomyoma |
| title_full | Chromatin state origins of uterine leiomyoma |
| title_fullStr | Chromatin state origins of uterine leiomyoma |
| title_full_unstemmed | Chromatin state origins of uterine leiomyoma |
| title_short | Chromatin state origins of uterine leiomyoma |
| title_sort | chromatin state origins of uterine leiomyoma |
| url | https://doi.org/10.1038/s41467-025-59646-w |
| work_keys_str_mv | AT marittaraisanen chromatinstateoriginsofuterineleiomyoma AT eevikaasinen chromatinstateoriginsofuterineleiomyoma AT maijajantti chromatinstateoriginsofuterineleiomyoma AT aurorataira chromatinstateoriginsofuterineleiomyoma AT emmasiili chromatinstateoriginsofuterineleiomyoma AT ralfbutzow chromatinstateoriginsofuterineleiomyoma AT oskariheikinheimo chromatinstateoriginsofuterineleiomyoma AT annukkapasanen chromatinstateoriginsofuterineleiomyoma AT aulikarhu chromatinstateoriginsofuterineleiomyoma AT finngen chromatinstateoriginsofuterineleiomyoma AT davidegberta chromatinstateoriginsofuterineleiomyoma AT nikovalimaki chromatinstateoriginsofuterineleiomyoma AT lauriaaaltonen chromatinstateoriginsofuterineleiomyoma |