Cohesin-mediated chromatin remodeling controls the differentiation and function of conventional dendritic cells DOI Creative Commons
Nicholas M. Adams, Aleksandra A. Galitsyna, Ioanna Tiniakou

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 22, 2024

Abstract The cohesin protein complex extrudes chromatin loops, stopping at CTCF-bound sites, to organize chromosomes into topologically associated domains, yet the biological implications of this process are poorly understood. We show that is required for post-mitotic differentiation and function antigen-presenting dendritic cells (DCs), particularly antigen cross-presentation IL-12 secretion by type 1 conventional DCs (cDC1s) in vivo . organization was shaped DC-specifying transcription factor IRF8, which controlled looping chromosome compartmentalization, respectively. Notably, optimal expression IRF8 itself CTCF/cohesin-binding sites demarcating Irf8 gene. During DC activation, induction a subset genes with distal enhancers. Accordingly, deletion CTCF flanking Il12b gene reduced production cDC1s. Our data reveal an essential role cohesin-mediated regulation cell , its bi-directional crosstalk lineage-specifying factors.

Language: Английский

Epigenetic regulatory layers in the 3D nucleus DOI Creative Commons
Andréa Willemin, Dominik Szabó, Ana Pombo

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(3), P. 415 - 428

Published: Jan. 18, 2024

Nearly 7 decades have elapsed since Francis Crick introduced the central dogma of molecular biology, as part his ideas on protein synthesis, setting fundamental rules sequence information transfer from DNA to RNAs and proteins. We learned that gene expression is finely tuned in time space, due activities proteins regulatory elements, through cell-type-specific three-dimensional conformations genome. Here, we review major advances genome biology discuss a set regulation highlight how various biomolecular assemblies lead formation structural features within nucleus, with roles transcriptional control. conclude by suggesting further developments will help capture complex, dynamic, often spatially restricted events govern mammalian cells.

Language: Английский

Citations

19
Modern biology of extrachromosomal DNA: A decade-long voyage of discovery DOI Creative Commons
Qinglin Yang, Yulei Xie,

Kailiang Qiao

et al.

Cell Research, Journal Year: 2025, Volume and Issue: 35(1), P. 11 - 22

Published: Jan. 3, 2025

Abstract Genomic instability is a hallmark of cancer and major driving force tumorigenesis. A key manifestation genomic the formation extrachromosomal DNAs (ecDNAs) — acentric, circular DNA molecules ranging from 50 kb to 5 Mb in size, distinct chromosomes. Ontological studies have revealed that ecDNA serves as carrier oncogenes, immunoregulatory genes, enhancers, capable elevated transcription its cargo genes heterogeneity, leading rapid tumor evolution therapy resistance. Although was documented over half century ago, past decade has witnessed surge breakthrough discoveries about biological functions. Here, we systematically review modern biology uncovered last ten years, focusing on how during this pioneering stage illuminated our understanding ecDNA-driven transcription, progression. Furthermore, discuss ongoing efforts target novel approach therapy. This burgeoning field entering new phase, poised reshape knowledge therapeutic strategies.

Language: Английский

Citations

5
Unveiling the mechanism of micro-and-nano plastic phytotoxicity on terrestrial plants: A comprehensive review of omics approaches DOI Creative Commons

Asad Jamil,

Ambreen Ahmad,

Muhammad Moeen-Ud-Din

et al.

Environment International, Journal Year: 2025, Volume and Issue: 195, P. 109257 - 109257

Published: Jan. 1, 2025

Micro-and-nano plastics (MNPs) are pervasive in terrestrial ecosystems and represent an increasing threat to plant health; however, the mechanisms underlying their phytotoxicity remain inadequately understood. MNPs can infiltrate plants through roots or leaves, causing a range of toxic effects, including inhibiting water nutrient uptake, reducing seed germination rates, impeding photosynthesis, resulting oxidative damage within system. The effects complex influenced by various factors size, shape, functional groups, concentration. Recent advancements omics technologies such as proteomics, metabolomics, transcriptomics, microbiomics, coupled with emerging like 4D omics, phenomics, spatial single-cell offer unprecedented insight into physiological, molecular, cellular responses exposure. This literature review synthesizes current findings regarding MNPs-induced phytotoxicity, emphasizing alterations gene expression, protein synthesis, metabolic pathways, physiological disruptions revealed analyses. We summarize how interact structures, disrupt processes, induce stress, ultimately affecting growth productivity. Furthermore, we have identified critical knowledge gaps proposed future research directions, highlighting necessity for integrative studies elucidate pathways toxicity plants. In conclusion, this underscores potential approaches MNPs-phytotoxicity develop strategies mitigating environmental impact on health.

Language: Английский

Citations

2
MYC phase separation selectively modulates the transcriptome DOI
Junjiao Yang, Chan-I Chung, Jessica Koach

et al.

Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: 31(10), P. 1567 - 1579

Published: May 29, 2024

Language: Английский

Citations

16
The evolution of developmental biology through conceptual and technological revolutions DOI Creative Commons
Prisca Liberali, Alexander F. Schier

Cell, Journal Year: 2024, Volume and Issue: 187(14), P. 3461 - 3495

Published: June 20, 2024

Developmental biology-the study of the processes by which cells, tissues, and organisms develop change over time-has entered a new golden age. After molecular genetics revolution in 80s 90s diversification field early 21st century, we have phase when powerful technologies provide approaches open unexplored avenues. Progress has been accelerated advances genomics, imaging, engineering, computational biology emerging model systems ranging from tardigrades to organoids. We summarize how revolutionary led remarkable progress understanding animal development. describe classic questions gene regulation, pattern formation, morphogenesis, organogenesis, stem cell are being revisited. discuss connections development with evolution, self-organization, metabolism, time, ecology. speculate developmental might evolve an era synthetic biology, artificial intelligence, human engineering.

Language: Английский

Citations

11
The chromosome folding problem and how cells solve it DOI Creative Commons
Job Dekker, Leonid A. Mirny

Cell, Journal Year: 2024, Volume and Issue: 187(23), P. 6424 - 6450

Published: Nov. 1, 2024

Every cell must solve the problem of how to fold its genome. We describe folded state chromosomes is result combined activity multiple conserved mechanisms. Homotypic affinity-driven interactions lead spatial partitioning active and inactive loci. Molecular motors through loop extrusion. Topological features such as supercoiling entanglements contribute chromosome folding dynamics, tethering loci sub-nuclear structures adds additional constraints. Dramatically diverse conformations observed throughout cycle across tree life can be explained differential regulation implementation these basic propose that first functions are mediate genome replication, compaction, segregation mechanisms have subsequently been co-opted for other roles, including long-range gene regulation, in different conditions, types, species.

Language: Английский

Citations

10
Viral remodeling of the 4D nucleome DOI Creative Commons
Kyoung-Dong Kim, Paul M. Lieberman

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(4), P. 799 - 808

Published: April 25, 2024

Abstract The dynamic spatial organization of genomes across time, referred to as the four-dimensional nucleome (4DN), is a key component gene regulation and biological fate. Viral infections can lead reconfiguration viral host genomes, impacting expression, replication, latency, oncogenic transformation. This review provides summary recent research employing three-dimensional genomic methods such Hi–C, 4C, ChIA-PET, HiChIP in virology. We how viruses induce changes loop formation between regulatory elements, modify chromatin accessibility, trigger shifts A B compartments genome. highlight central role cellular organizing factors, CTCF cohesin, that reshape 3D structure both genomes. consider episomes, proteins, integration sites alter epigenome cell type conditions determine epigenomes. consolidates current knowledge diverse host-viral interactions impact 4DN.

Language: Английский

Citations

9
Dynamic histone modification patterns coordinating DNA processes DOI

Laura López-Hernández,

Patrick Toolan-Kerr, Andrew J. Bannister

et al.

Molecular Cell, Journal Year: 2025, Volume and Issue: 85(2), P. 225 - 237

Published: Jan. 1, 2025

Language: Английский

Citations

1
Genome-wide absolute quantification of chromatin looping DOI Creative Commons
James M. Jusuf, Simon Grosse‐Holz, Michele Gabriele

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

3D genomics methods such as Hi-C and Micro-C have uncovered chromatin loops across the genome linked these to gene regulation. However, only measure interaction probabilities on a relative scale. Here, we overcome this limitation by using live imaging data calibrate in mouse embryonic stem cells, thus obtaining absolute looping for 36,804 genome. We find that looped state is generally rare, with mean probability of 2.3% maximum 26% quantified loops. On average, CTCF-CTCF are stronger than between cis-regulatory elements (3.2% vs. 1.1%). Our findings can be extended human cells differentiated under certain assumptions. Overall, establish an approach genome-wide loop quantification report occur low probabilities, generalizing recent results whole

Language: Английский

Citations

1
Cell type–specific 3D-genome organization and transcription regulation in the brain DOI Creative Commons

Shiwei Liu,

Cosmos Yuqi Wang, Pu Zheng

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(9)

Published: Feb. 26, 2025

3D organization of the genome plays a critical role in regulating gene expression. How 3D-genome differs among different cell types and relates to type–dependent transcriptional regulation remains unclear. Here, we used genome-scale DNA RNA imaging investigate transcriptionally distinct mouse cerebral cortex. We uncovered wide spectrum differences nuclear architecture types, ranging from size nucleus higher-order chromosome structures radial positioning chromatin loci within nucleus. These variations exhibit strong correlations with both total activity type–specific marker genes. Moreover, found that methylated binding protein MeCP2 promotes active-inactive segregation regulates transcription position–dependent manner is highly correlated its function modulating compartmentalization.

Language: Английский

Citations

1