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(2023)", "@id": "/publications/5946fa1d-a501-4676-a602-cc28cad65a8b/", "date_published": "2023-06-19", "uuid": "5946fa1d-a501-4676-a602-cc28cad65a8b", "authors": ["Beagrie RA", "Thieme CJ", "Annunziatella C", "Baugher C", "Zhang Y", "Schueler M", "Kukalev A", "Kempfer R", "Chiariello AM", "Bianco S", "Li Y", "Davis T", "Scialdone A", "Welch LR", "Nicodemi M", "Pombo A"], "abstract": "Technology for measuring 3D genome topology is increasingly important for  studying gene regulation, for genome assembly and for mapping of genome  rearrangements. Hi-C and other ligation-based methods have become routine but  have specific biases. Here, we develop multiplex-GAM, a faster and more  affordable version of genome architecture mapping (GAM), a ligation-free  technique that maps chromatin contacts genome-wide. We perform a detailed  comparison of multiplex-GAM and Hi-C using mouse embryonic stem cells. When  examining the strongest contacts detected by either method, we find that only  one-third of these are shared. The strongest contacts specifically found in GAM  often involve 'active' regions, including many transcribed genes and  super-enhancers, whereas in Hi-C they more often contain 'inactive' regions. Our  work shows that active genomic regions are involved in extensive complex contacts  that are currently underestimated in ligation-based approaches, and highlights  the need for orthogonal advances in genome-wide contact mapping technologies.", "title": "Multiplex-GAM: genome-wide identification of chromatin contacts yields insights  overlooked by Hi-C.", "ID": "PMID:37336949", "@type": ["Publication", "Item"], "status": "current", "display_title": "Beagrie RA et al. (2023) PMID:37336949", "journal": "Nature methods", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "publications_of_exp": [{"title": "Cell-type specialization is encoded by specific chromatin topologies.", "date_published": "2021-11", "display_title": "Winick-Ng W et al. (2021) PMID:34789882", "short_attribution": "Winick-Ng W et al. (2021)", "authors": ["Winick-Ng W", "Kukalev A", "Harabula I", "Zea-Redondo L", "Szabo D", "Meijer M", "Serebreni L", "Zhang Y", "Bianco S", "Chiariello AM", "Irastorza-Azcarate I", "Thieme CJ", "Sparks TM", "Carvalho S", "Fiorillo L", "Musella F", "Irani E", "Triglia ET", "Kolodziejczyk AA", "Abentung A", "Apostolova G", "Paul EJ", "Franke V", "Kempfer R", "Akalin A", "Teichmann SA", "Dechant G", "Ungless MA", "Nicodemi M", "Welch L", "Castelo-Branco G", "Pombo A"], "ID": "PMID:34789882", "@type": ["Publication", "Item"], "uuid": "613340da-ecdc-44bd-ae74-437b2ad65ac6", "@id": "/publications/613340da-ecdc-44bd-ae74-437b2ad65ac6/", "abstract": "The three-dimensional (3D) structure of chromatin is intrinsically associated with gene regulation and cell function(1-3). Methods based on chromatin conformation capture have mapped chromatin structures in neuronal systems such as in vitro differentiated neurons, neurons isolated through fluorescence-activated  cell sorting from cortical tissues pooled from different animals and from dissociated whole hippocampi(4-6). However, changes in chromatin organization captured by imaging, such as the relocation of Bdnf away from the nuclear periphery after activation(7), are invisible with such approaches(8). Here we developed immunoGAM, an extension of genome architecture mapping (GAM)(2,9), to map 3D chromatin topology genome-wide in specific brain cell types, without tissue disruption, from single animals. GAM is a ligation-free technology that maps genome topology by sequencing the DNA content from thin (about 220 nm) nuclear cryosections. Chromatin interactions are identified from the increased probability of co-segregation of contacting loci across a collection of nuclear slices. ImmunoGAM expands the scope of GAM to enable the selection of specific cell types using low cell numbers (approximately 1,000 cells) within a complex tissue and avoids tissue dissociation(2,10). We report cell-type specialized 3D chromatin structures at multiple genomic scales that relate to patterns of gene expression. We discover extensive 'melting' of long genes when they are highly expressed and/or have high chromatin accessibility. The contacts most specific of neuron subtypes contain genes associated with specialized processes, such as addiction and synaptic plasticity, which harbour putative binding sites for neuronal transcription factors within accessible chromatin regions. Moreover, sensory receptor genes are preferentially found in heterochromatic compartments in brain cells, which establish strong contacts across tens of megabases. Our results demonstrate that highly specific chromatin conformations in brain cells are tightly related to gene regulation mechanisms and specialized functions.", "status": "current", "journal": "Nature", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"title": "A single dose of cocaine rewires the 3D genome structure of midbrain dopamine  neurons.", "date_published": "2024-05-12", "display_title": "Szabo D et al. (2024) PMID:38766140", "short_attribution": "Szabo D et al. (2024)", "authors": ["Szabo D", "Franke V", "Bianco S", "Batiuk MY", "Paul EJ", "Kukalev A", "Pfisterer UG", "Irastorza-Azcarate I", "Chiariello AM", "Demharter S", "Zea-Redondo L", "Lopez-Atalaya JP", "Nicodemi M", "Akalin A", "Khodosevich K", "Ungless MA", "Winick-Ng W", "Pombo A"], "ID": "PMID:38766140", "@type": ["Publication", "Item"], "uuid": "53947f85-e28f-405f-b92e-92ca7bdb2aea", "@id": "/publications/53947f85-e28f-405f-b92e-92ca7bdb2aea/", "abstract": "Midbrain dopamine neurons (DNs) respond to a first exposure to addictive drugs  and play key roles in chronic drug usage (1-3) . As the synaptic and  transcriptional changes that follow an acute cocaine exposure are mostly resolved  within a few days (4,5) , the molecular changes that encode the long-term  cellular memory of the exposure within DNs remain unknown. To investigate whether  a single cocaine exposure induces long-term changes in the 3D genome structure of  DNs, we applied Genome Architecture Mapping and single nucleus transcriptomic  analyses in the mouse midbrain. We found extensive rewiring of 3D genome  architecture at 24 hours past exposure which remains or worsens by 14 days,  outlasting transcriptional responses. The cocaine-induced chromatin rewiring  occurs at all genomic scales and affects genes with major roles in  cocaine-induced synaptic changes. A single cocaine exposure triggers extensive  long-lasting changes in chromatin condensation in post-synaptic and  post-transcriptional regulatory genes, for example the unfolding of Rbfox1 which  becomes most prominent 14 days post exposure. Finally, structurally remodeled  genes are most expressed in a specific DN sub-type characterized by low  expression of the dopamine auto-receptor Drd2 , a key feature of highly  cocaine-sensitive cells. These results reveal an important role for long-lasting  3D genome remodelling in the cellular memory of a single cocaine exposure,  providing new hypotheses for understanding the inception of drug addiction and 3D  genome plasticity.", "status": "current", "journal": "bioRxiv : the preprint server for biology", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"title": "Multiplex-GAM: genome-wide identification of chromatin contacts yields insights  overlooked by Hi-C.", "date_published": "2023-06-19", "display_title": "Beagrie RA et al. (2023) PMID:37336949", "short_attribution": "Beagrie RA et al. (2023)", "authors": ["Beagrie RA", "Thieme CJ", "Annunziatella C", "Baugher C", "Zhang Y", "Schueler M", "Kukalev A", "Kempfer R", "Chiariello AM", "Bianco S", "Li Y", "Davis T", "Scialdone A", "Welch LR", "Nicodemi M", "Pombo A"], "ID": "PMID:37336949", "@type": ["Publication", "Item"], "uuid": "5946fa1d-a501-4676-a602-cc28cad65a8b", "@id": "/publications/5946fa1d-a501-4676-a602-cc28cad65a8b/", "abstract": "Technology for measuring 3D genome topology is increasingly important for  studying gene regulation, for genome assembly and for mapping of genome  rearrangements. Hi-C and other ligation-based methods have become routine but  have specific biases. Here, we develop multiplex-GAM, a faster and more  affordable version of genome architecture mapping (GAM), a ligation-free  technique that maps chromatin contacts genome-wide. We perform a detailed  comparison of multiplex-GAM and Hi-C using mouse embryonic stem cells. When  examining the strongest contacts detected by either method, we find that only  one-third of these are shared. The strongest contacts specifically found in GAM  often involve 'active' regions, including many transcribed genes and  super-enhancers, whereas in Hi-C they more often contain 'inactive' regions. Our  work shows that active genomic regions are involved in extensive complex contacts  that are currently underestimated in ligation-based approaches, and highlights  the need for orthogonal advances in genome-wide contact mapping technologies.", "status": "current", "journal": "Nature methods", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "experiment_categorizer": {"field": "Default", "value": null}, "experiment_summary": "GAM on 46C with Sox1-GFP", "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/biosamples/4DNBSXU4PXTD/", "embedded_path": "biosample.badges", "item": {"messages": ["Biosample missing Cell Culture Details"], "badge": {"commendation": null, "warning": "Biosample Metadata Incomplete", "uuid": "2b2cc7ff-b7a8-4138-9a6c-22884fc71690", "@id": "/badges/biosample-metadata-incomplete/", "badge_icon": "/static/img/badges/biosample-icon.svg", "description": "Biosample is missing metadata information required as part of the standards implemented by the 4DN Samples working group."}}}]}, "validation-errors": []}