| Title: | Chromatin state origins of uterine leiomyoma |
| Journal: | Nature Communications |
| Published: | 8 May 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40341524/ |
| DOI: | https://doi.org/10.1038/s41467-025-59646-w |
Publication 15396
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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.</p>
14 Keywords
- Chromatin
- DNA Methylation
- Epigenome
- Female
- Gene Expression Regulation, Neoplastic
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Leiomyoma
- Matrix Attachment Region Binding Proteins
- Mutation
- Myometrium
- Transcription Factors
- Uterine Neoplasms
12 Authors
- Maritta Räisänen
- Eevi Kaasinen
- Maija Jäntti
- Aurora Taira
- Emma Siili
- Ralf Bützow
- Oskari Heikinheimo
- Annukka Pasanen
- Auli Karhu
- Davide G. Berta
- Niko Välimäki
- Lauri A. Aaltonen
1 Application
| Application ID | Title |
|---|---|
| 80756 | Germline genetic, socioeconomic and medical risk factors of tumorigenesis |
Enabling scientific discoveries that improve human health