aBIOTECH, Journal Year: 2025, Volume and Issue: unknown
Published: March 26, 2025
Language: Английский
Cell, Journal Year: 2024, Volume and Issue: 187(17), P. 4520 - 4545
Published: Aug. 1, 2024
Language: Английский
Citations
26
Nature, Journal Year: 2024, Volume and Issue: 634(8036), P. 1211 - 1220
Published: Oct. 23, 2024
Cis-regulatory elements (CREs) control gene expression, orchestrating tissue identity, developmental timing and stimulus responses, which collectively define the thousands of unique cell types in body
Language: Английский
Citations
26
Nature, Journal Year: 2024, Volume and Issue: 633(8028), P. 47 - 57
Published: Sept. 4, 2024
Language: Английский
Citations
24
Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: 31(3), P. 559 - 567
Published: March 1, 2024
Language: Английский
Citations
11
Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)
Published: April 11, 2024
Abstract The epigenome—the chemical modifications and chromatin-related packaging of the genome—enables same genetic template to be activated or repressed in different cellular settings. This multi-layered mechanism facilitates cell-type specific function by setting local sequence 3D interactive activity level. Gene transcription is further modulated through interplay with factors co-regulators. human body requires this epigenomic apparatus precisely installed throughout development then adequately maintained during lifespan. causal role epigenome pathology, beyond imprinting disorders tumour suppressor genes, was brought into spotlight large-scale sequencing projects identifying that mutations machinery genes could critical drivers both cancer developmental disorders. Abrogation providing new molecular insights pathogenesis. However, deciphering full breadth implications these changes remains challenging. Knowledge accruing regarding disease mechanisms clinical biomarkers, pathogenically relevant surrogate tissue analyses, respectively. Advances include consortia generated reference epigenomes, high-throughput DNA methylome association studies, as well ageing-related diseases from biological ‘clocks’ constructed machine learning algorithms. Also, 3rd-generation beginning disentangle complexity modification haplotypes. Cell-free methylation a biomarker has clear utility potential assess organ damage across many Finally, understanding aetiology brings it opportunity for exact therapeutic alteration CRISPR-activation inhibition.
Language: Английский
Citations
11
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: March 27, 2025
Abstract The establishment of germ layers during early development is crucial for body formation. Drosophila zygote serves as a model investigating these transitions in relation to the chromatin landscape. However, cellular heterogeneity blastoderm embryo poses challenge gaining mechanistic insights. Using 10× Multiome, we simultaneously analyzed vivo epigenomic and transcriptomic states wild-type, E(z)-, CBP-depleted embryos zygotic genome activation at single-cell resolution. We found that pre-zygotic H3K27me3 safeguards tissue-specific gene expression by modulating cis -regulatory elements. Furthermore, demonstrate CBP essential cell fate specification functioning transcriptional activator stabilizing factors binding key developmental genes. Surprisingly, while depletion leads arrest, accessibility continues progress independently through retention stalled RNA Polymerase II. Our study reveals fundamental principles chromatin-mediated regulation establishing maintaining identities embryogenesis.
Language: Английский
Citations
2
Molecular Cell, Journal Year: 2024, Volume and Issue: 84(18), P. 3455 - 3468.e6
Published: Aug. 28, 2024
Language: Английский
Citations
8
Cell Systems, Journal Year: 2025, Volume and Issue: unknown, P. 101163 - 101163
Published: Jan. 1, 2025
Highlights•Transcription factor binding sites activate or repress depending on context•Genomic examples are insufficient to learn how context affects sites•Active learning iteratively generates informative new training data•A CNN trained with active distinguishes activating and repressing sitesSummaryDeep is a promising strategy for modeling cis-regulatory elements. However, models genomic sequences often fail explain why the same transcription can in different contexts. To address this limitation, we developed an approach train that distinguish between enhancers silencers composed of photoreceptor cone-rod homeobox (CRX). After model nearly all bound CRX from genome, coupled synthetic biology uncertainty sampling generate additional rounds data. This allowed us data multiple massively parallel reporter assays. The ability resulting discriminate identical sequence but opposite functions establishes as effective regulatory DNA. A record paper's transparent peer review process included supplemental information.Graphical abstract
Language: Английский
Citations
1
Nature, Journal Year: 2025, Volume and Issue: unknown
Published: April 9, 2025
Language: Английский
Citations
1
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Feb. 18, 2024
Cis-regulatory elements (CREs), such as promoters and enhancers, are DNA sequences that regulate the expression of genes. The activity a CRE is influenced by order, composition spacing sequence motifs bind to proteins called transcription factors (TFs). Synthetic CREs with specific properties needed for biomanufacturing well many therapeutic applications including cell gene therapy. Here, we present regLM, framework design synthetic desired properties, high, low or type-specific activity, using autoregressive language models in conjunction supervised sequence-to-function models. We used our yeast human enhancers. demonstrate generated approach not only predicted have functionality but also contain biological features similar experimentally validated CREs. regLM thus facilitates realistic regulatory while providing insights into cis-regulatory code.
Language: Английский
Citations
6