Primary osteoarthritis chondrocyte map of chromatin conformation reveals novel candidate effector genes DOI Creative Commons
Norbert Bittner, Chenfu Shi, Danyun Zhao

et al.

Annals of the Rheumatic Diseases, Journal Year: 2024, Volume and Issue: 83(8), P. 1048 - 1059

Published: March 13, 2024

Osteoarthritis is a complex disease with huge public health burden. Genome-wide association studies (GWAS) have identified hundreds of osteoarthritis-associated sequence variants, but the effector genes underpinning these signals remain largely elusive. Understanding chromosome organisation in three-dimensional (3D) space essential for identifying long-range contacts between distant genomic features (e.g., and regulatory elements), tissue-specific manner. Here, we generate first whole genome conformation analysis (Hi-C) map primary osteoarthritis chondrocytes identify novel candidate disease.

Language: Английский

Topological structures and syntenic conservation in sea anemone genomes DOI Creative Commons
Bob Zimmermann, Juan D. Montenegro, Sofia Robb

et al.

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

Published: Dec. 13, 2023

Abstract There is currently little information about the evolution of gene clusters, genome architectures and karyotypes in early branching animals. Slowly evolving anthozoan cnidarians can be particularly informative these features. Here we report chromosome-level assemblies two related anthozoans, sea anemones Nematostella vectensis Scolanthus callimorphus . We find a robust set 15 chromosomes with clear one-to-one correspondence between species. Both genomes show chromosomal conservation, allowing us to reconstruct ancestral cnidarian metazoan blocks, consisting at least 19 16 linkage groups, respectively. that, contrast Bilateria, Hox NK clusters investigated are largely disintegrated, despite presence staggered hox/gbx expression This loss microsynteny conservation may facilitated by shorter distances cis-regulatory sequences their cognate transcriptional start sites. no evidence for topologically associated domains, suggesting fundamental differences long-range regulation compared vertebrates. These data suggest that large sets genes have been retained groups some extant lineages; yet, higher order 3D architecture evolved only after cnidarian-bilaterian split.

Language: Английский

Citations

33

High-throughput Pore-C reveals the single-allele topology and cell type-specificity of 3D genome folding DOI Creative Commons
Jiayong Zhong, Longjian Niu,

Zhuobin Lin

et al.

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

Published: March 6, 2023

Abstract Canonical three-dimensional (3D) genome structures represent the ensemble average of pairwise chromatin interactions but not single-allele topologies in populations cells. Recently developed Pore-C can capture multiway contacts that reflect regional single chromosomes. By carrying out high-throughput Pore-C, we reveal extensive regionally restricted clusters aggregate into canonical 3D two human cell types. We show fragments multi-contact reads generally coexist same TAD. In contrast, a concurrent significant proportion span multiple compartments type over megabase distances. Synergistic looping between sites is rare compared to interactions. Interestingly, topology are type-specific even inside highly conserved TADs different types summary, HiPore-C enables global characterization at an unprecedented depth elusive folding principles.

Language: Английский

Citations

31

Multiplex-GAM: genome-wide identification of chromatin contacts yields insights overlooked by Hi-C DOI Creative Commons
Robert A. Beagrie, Christoph J. Thieme, Carlo Annunziatella

et al.

Nature Methods, Journal Year: 2023, Volume and Issue: 20(7), P. 1037 - 1047

Published: June 19, 2023

Abstract Technology for measuring 3D genome topology is increasingly important studying gene regulation, assembly and mapping of rearrangements. Hi-C other ligation-based methods have become routine but specific biases. Here, we develop multiplex-GAM, a faster more affordable version architecture (GAM), ligation-free technique that maps chromatin contacts genome-wide. We perform detailed comparison multiplex-GAM using mouse embryonic stem cells. When examining the strongest detected by either method, find only one-third these are shared. The specifically found in GAM often involve ‘active’ regions, including many transcribed genes super-enhancers, whereas they contain ‘inactive’ regions. Our work shows active genomic regions involved extensive complex currently underestimated approaches, highlights need orthogonal advances genome-wide contact technologies.

Language: Английский

Citations

27

ZNF143 deletion alters enhancer/promoter looping and CTCF/cohesin geometry DOI Creative Commons
Mo Zhang, Haiyan Huang, Jingwei Li

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(1), P. 113663 - 113663

Published: Jan. 1, 2024

The transcription factor ZNF143 contains a central domain of seven zinc fingers in tandem array and is involved 3D genome construction. However, the mechanism by which functions chromatin looping remains unclear. Here, we show that directionally recognizes diverse range genomic sites directly within enhancers promoters required for between these sites. In addition, located CTCF cohesin at numerous sites, removal narrows space cohesin. Moreover, genetic deletion ZNF143, conjunction with acute degradation, reveals collaborate to regulate higher-order topological organization. Finally, depletion enlarges direct looping. Thus, recruited CTCF/cohesin configuration TAD (topologically associating domain) formation, whereas directional recognition DNA motifs itself regulates promoter activity via

Language: Английский

Citations

16

Primary osteoarthritis chondrocyte map of chromatin conformation reveals novel candidate effector genes DOI Creative Commons
Norbert Bittner, Chenfu Shi, Danyun Zhao

et al.

Annals of the Rheumatic Diseases, Journal Year: 2024, Volume and Issue: 83(8), P. 1048 - 1059

Published: March 13, 2024

Osteoarthritis is a complex disease with huge public health burden. Genome-wide association studies (GWAS) have identified hundreds of osteoarthritis-associated sequence variants, but the effector genes underpinning these signals remain largely elusive. Understanding chromosome organisation in three-dimensional (3D) space essential for identifying long-range contacts between distant genomic features (e.g., and regulatory elements), tissue-specific manner. Here, we generate first whole genome conformation analysis (Hi-C) map primary osteoarthritis chondrocytes identify novel candidate disease.

Language: Английский

Citations

16