Current Biology, Год журнала: 2025, Номер unknown
Опубликована: Март 1, 2025
Язык: Английский
Current Biology, Год журнала: 2025, Номер unknown
Опубликована: Март 1, 2025
Язык: Английский
International Journal of Biological Macromolecules, Год журнала: 2024, Номер 265, С. 130659 - 130659
Опубликована: Март 11, 2024
Язык: Английский
Процитировано
10Molecular Systems Biology, Год журнала: 2024, Номер 20(5), С. 573 - 589
Опубликована: Март 26, 2024
Язык: Английский
Процитировано
10PLoS Biology, Год журнала: 2025, Номер 23(1), С. e3002950 - e3002950
Опубликована: Янв. 6, 2025
In many eukaryotes, meiotic recombination occurs preferentially at discrete sites, called hotspots. various lineages, hotspots are located in regions with promoter-like features and evolutionarily stable. Conversely, some mammals, driven by PRDM9 that targets away from promoters. Paradoxically, induces the self-destruction of its this triggers an ultra-fast evolution mammalian is ancestral to all animals, suggesting a critical importance for program, but has been lost lineages surprisingly little effect on meiosis success. However, it unclear whether function described mammals shared other species. To investigate this, we analyzed landscape several salmonids, genome which harbors one full-length truncated paralogs. We identified initiation sites Oncorhynchus mykiss mapping DNA double-strand breaks (DSBs). found DSBs clustered positioned promoters, enriched H3K4me3 H3K36me3 location depended genotype Prdm9 . observed high level polymorphism zinc finger domain , indicating diversification positive selection. Moreover, population-scaled maps O kisutch Salmo salar revealed rapid turnover caused target motif erosion. Our results imply conserved across vertebrates peculiar evolutionary runaway active hundred million years.
Язык: Английский
Процитировано
1Nature, Год журнала: 2025, Номер unknown
Опубликована: Янв. 15, 2025
Abstract The human genome contains millions of candidate cis -regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states 1 . However, we lack a functional understanding the sequence features control activity these cCREs. Here used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test regulatory more than 680,000 sequences, representing an extensive set annotated cCREs among three cell types (HepG2, K562 WTC11), found 41.7% sequences were active. By testing in orientations, find promoters have strand-orientation biases their 200-nucleotide cores function as non-cell-type-specific ‘on switches’ provide similar expression levels associated gene. contrast, enhancers weaker orientation biases, but increased tissue-specific characteristics. Utilizing our lentiMPRA data, develop sequence-based models predict cCRE variant effects high accuracy, delineate motifs model combinatorial effects. Testing library encompassing 60,000 all further identified factors determine cell-type specificity. Collectively, work provides catalogue CREs widely lines showcases how large-scale measurements can be dissect grammar.
Язык: Английский
Процитировано
1Current Biology, Год журнала: 2025, Номер unknown
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
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