Author
Listed:
- Maritta Räisänen
(University of Helsinki
University of Helsinki)
- Eevi Kaasinen
(University of Helsinki
University of Helsinki)
- Maija Jäntti
(University of Helsinki
University of Helsinki)
- Aurora Taira
(University of Helsinki
University of Helsinki)
- Emma Siili
(University of Helsinki and Helsinki University Hospital)
- Ralf Bützow
(University of Helsinki
University of Helsinki and Helsinki University Hospital)
- Oskari Heikinheimo
(University of Helsinki and Helsinki University Hospital)
- Annukka Pasanen
(University of Helsinki and Helsinki University Hospital)
- Auli Karhu
(University of Helsinki
University of Helsinki)
- Davide G. Berta
(University of Helsinki
University of Helsinki)
- Niko Välimäki
(University of Helsinki
University of Helsinki)
- Lauri A. Aaltonen
(University of Helsinki
University of Helsinki
University of Helsinki)
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.
Suggested Citation
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, 2025.
"Chromatin state origins of uterine leiomyoma,"
Nature Communications, Nature, vol. 16(1), pages 1-16, December.
Handle:
RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59646-w
DOI: 10.1038/s41467-025-59646-w
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