Drug-Induced Epigenomic Plasticity Reprograms Circadian Rhythm Regulation to Drive Prostate Cancer toward Androgen Independence DOI
Simon Linder, Marlous Hoogstraat, Suzan Stelloo

et al.

Cancer Discovery, Journal Year: 2022, Volume and Issue: 12(9), P. 2074 - 2097

Published: June 27, 2022

In prostate cancer, androgen receptor (AR)-targeting agents are very effective in various disease stages. However, therapy resistance inevitably occurs, and little is known about how tumor cells adapt to bypass AR suppression. Here, we performed integrative multiomics analyses on tissues isolated before after 3 months of AR-targeting enzalutamide monotherapy from patients with high-risk cancer enrolled a neoadjuvant clinical trial. Transcriptomic demonstrated that inhibition drove tumors toward neuroendocrine-like state. Additionally, epigenomic profiling revealed massive enzalutamide-induced reprogramming pioneer factor FOXA1 inactive chromatin sites active cis-regulatory elements dictate prosurvival signals. Notably, treatment-induced were enriched for the circadian clock component ARNTL. Posttreatment ARNTL levels associated patients' outcomes, knockout strongly decreased cell growth. Our data highlight remarkable cistromic plasticity following AR-targeted an acquired dependency regulator ARNTL, novel candidate therapeutic target.Understanding cancers interventions critical identifying drug targets improve management treatment-resistant disease. study signaling uncovered as vulnerability inhibition, presenting lead development. See related commentary by Zhang et al., p. 2017. This article highlighted Issue feature, 2007.

Language: Английский

Genome evolution and diversity of wild and cultivated potatoes DOI Creative Commons
Dié Tang, Yuxin Jia, Jinzhe Zhang

et al.

Nature, Journal Year: 2022, Volume and Issue: 606(7914), P. 535 - 541

Published: June 8, 2022

Potato (Solanum tuberosum L.) is the world's most important non-cereal food crop, and vast majority of commercially grown cultivars are highly heterozygous tetraploids. Advances in diploid hybrid breeding based on true seeds have potential to revolutionize future potato production1-4. So far, relatively few studies examined genome evolution diversity wild cultivated landrace potatoes, which limits application their breeding. Here we assemble 44 high-quality genomes from 24 20 accessions that representative Solanum section Petota, tuber-bearing clade, as well 2 neighbouring section, Etuberosum. Extensive discordance phylogenomic relationships suggests complexity evolution. We find substantially expanded its repertoire disease-resistance genes when compared with closely related seed-propagated solanaceous crops, indicative effect tuber-based propagation strategies genome. discover a transcription factor determines tuber identity interacts mobile tuberization inductive signal SP6A. also identify 561,433 high-confidence structural variants construct map large inversions, provides insights for improving inbred lines precluding linkage drag, exemplified by 5.8-Mb inversion associated carotenoid content tubers. This study will accelerate enrich our understanding biology global staple crop.

Language: Английский

Citations

242
A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors DOI Creative Commons

Anders B. Dohlman,

Jared Klug,

Marissa Mesko

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(20), P. 3807 - 3822.e12

Published: Sept. 1, 2022

Language: Английский

Citations

238
FAN-C: a feature-rich framework for the analysis and visualisation of chromosome conformation capture data DOI Creative Commons
Kai Kruse, Clemens B. Hug, Juan M. Vaquerizas

et al.

Genome biology, Journal Year: 2020, Volume and Issue: 21(1)

Published: Dec. 1, 2020

Chromosome conformation capture data, particularly from high-throughput approaches such as Hi-C, are typically very complex to analyse. Existing analysis tools often single-purpose, or limited in compatibility a small number of data formats, frequently making Hi-C analyses tedious and time-consuming. Here, we present FAN-C, an easy-to-use command-line tool powerful Python API with broad feature set covering matrix generation, analysis, visualisation for C-like ( https://github.com/vaquerizaslab/fanc ). Due its the most prevalent storage FAN-C can be used combination large existing tools, thus greatly simplifying analysis.

Language: Английский

Citations

169
A genome-scale screen for synthetic drivers of T cell proliferation DOI
Mateusz Legut, Zoran Gajic, Maria Guarino

et al.

Nature, Journal Year: 2022, Volume and Issue: 603(7902), P. 728 - 735

Published: March 16, 2022

Language: Английский

Citations

138
Repeat-based holocentromeres influence genome architecture and karyotype evolution DOI Creative Commons
Paulo G. Hofstatter, Gokilavani Thangavel, Thomas Lux

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(17), P. 3153 - 3168.e18

Published: Aug. 1, 2022

The centromere represents a single region in most eukaryotic chromosomes. However, several plant and animal lineages assemble holocentromeres along the entire chromosome length. Here, we compare genome organization evolution as function of type by assembling chromosome-scale holocentric genomes with repeat-based from three beak-sedge (Rhynchospora pubera, R. breviuscula, tenuis) their closest monocentric relative, Juncus effusus. We demonstrate that transition to holocentricity affected 3D architecture redefining genomic compartments, while distributing thousands units genome-wide. uncover complex pubera hides its unexpected octoploidy describe marked reduction number for tenuis, which has only two show fusions, facilitated holocentromeres, promoted karyotype diploidization. Our study thus sheds light on important aspects influenced organization.

Language: Английский

Citations

80
RNA polymerase II dynamics shape enhancer–promoter interactions DOI
Gilad Barshad, James J. Lewis, Alexandra G. Chivu

et al.

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(8), P. 1370 - 1380

Published: July 10, 2023

Language: Английский

Citations

73
Chromatin expansion microscopy reveals nanoscale organization of transcription and chromatin DOI
Mark E. Pownall, Liyun Miao, Charles E. Vejnar

et al.

Science, Journal Year: 2023, Volume and Issue: 381(6653), P. 92 - 100

Published: July 6, 2023

Nanoscale chromatin organization regulates gene expression. Although is notably reprogrammed during zygotic genome activation (ZGA), the of regulatory factors this universal process remains unclear. In work, we developed expansion microscopy (ChromExM) to visualize chromatin, transcription, and transcription in vivo. ChromExM embryos ZGA revealed how pioneer factor Nanog interacts with nucleosomes RNA polymerase II (Pol II), providing direct visualization transcriptional elongation as string-like nanostructures. Blocking led more Pol particles clustered around Nanog, stalled at promoters Nanog-bound enhancers. This a new model termed "kiss kick", which enhancer-promoter contacts are transient released by elongation. Our results demonstrate that broadly applicable study nanoscale nuclear organization.

Language: Английский

Citations

63
Annelid functional genomics reveal the origins of bilaterian life cycles DOI Creative Commons
Francisco M. Martín-Zamora, Yan Liang, Kero Guynes

et al.

Nature, Journal Year: 2023, Volume and Issue: 615(7950), P. 105 - 110

Published: Jan. 25, 2023

Language: Английский

Citations

62
CRISPR screens decode cancer cell pathways that trigger γδ T cell detection DOI
Murad R. Mamedov,

Shane Vedova,

Jacob W. Freimer

et al.

Nature, Journal Year: 2023, Volume and Issue: 621(7977), P. 188 - 195

Published: Aug. 30, 2023

Language: Английский

Citations

50
Single-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers DOI Creative Commons
Logan Brase, Shih‐Feng You, Ricardo D’Oliveira Albanus

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 21, 2023

Genetic studies of Alzheimer disease (AD) have prioritized variants in genes related to the amyloid cascade, lipid metabolism, and neuroimmune modulation. However, cell-specific effect these is not fully understood. Here, we perform single-nucleus RNA-sequencing (snRNA-seq) on nearly 300,000 nuclei from parietal cortex AD autosomal dominant (APP PSEN1) risk-modifying variant (APOE, TREM2 MS4A) carriers. Within individual cell types, capture commonly dysregulated across groups. specific transcriptional states are more prevalent within oligodendrocytes show a autophagy-lysosomal pathway, MS4A microglia complement cascade genes, APOEε4 inhibitory neurons display signs ferroptosis. All types enriched We leverage differential expression ATAC-seq map GWAS signals effector including NCK2 signal addition initially proposed microglia. Overall, our results provide insights into diversity resulting genetic architecture cellular heterogeneity. The data can be explored online browser ( http://web.hararilab.org/SNARE/ ).

Language: Английский

Citations

48