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NOTE The excel workbook downloadable from this page contains information that can be used to evaluate the quality of the GAM libraries linked to this dataset.

\n

The workbook consists of 2 sheets. The first provides descriptions and terms used in the second and highlights those that may be used to evaluate quality of the libraries. The second sheet provides information on each individual GAM library linked to this dataset. Each library corresponds to a single FastQ file that can be identified using the provided Sample_ID in the first column.

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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.", "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"], "status": "current", "date_published": "2021-11", "short_attribution": "Winick-Ng W et al. (2021)", "journal": "Nature", "display_title": "Winick-Ng W et al. (2021) PMID:34789882", "title": "Cell-type specialization is encoded by specific chromatin topologies.", "ID": "PMID:34789882", "@id": "/publications/613340da-ecdc-44bd-ae74-437b2ad65ac6/", "url": "https://www.ncbi.nlm.nih.gov/pubmed/34789882", "@type": ["Publication", "Item"], "uuid": "613340da-ecdc-44bd-ae74-437b2ad65ac6", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "pubs_using": [{"@type": ["Publication", "Item"], "display_title": "Szabo D et al. (2024) PMID:38766140", "status": "current", "@id": "/publications/53947f85-e28f-405f-b92e-92ca7bdb2aea/", "uuid": "53947f85-e28f-405f-b92e-92ca7bdb2aea", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "publications_of_set": [{"@id": "/publications/613340da-ecdc-44bd-ae74-437b2ad65ac6/", "display_title": "Winick-Ng W et al. (2021) PMID:34789882", "@type": ["Publication", "Item"], "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"], "date_published": "2021-11", "title": "Cell-type specialization is encoded by specific chromatin topologies.", "ID": "PMID:34789882", "journal": "Nature", "uuid": "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", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"@id": "/publications/53947f85-e28f-405f-b92e-92ca7bdb2aea/", "display_title": "Szabo D et al. (2024) PMID:38766140", "@type": ["Publication", "Item"], "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"], "date_published": "2024-05-12", "title": "A single dose of cocaine rewires the 3D genome structure of midbrain dopamine neurons.", "ID": "PMID:38766140", "journal": "bioRxiv : the preprint server for biology", "uuid": "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", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "number_of_experiments": 1, "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/experiment-set-replicates/4DNES2FWQBJW/", "embedded_path": "badges", "item": {"messages": ["Replicate set contains only a single biological replicate"], "badge": {"commendation": null, "warning": "Replicate Numbers", "uuid": "24a64a84-3c33-4d76-aaf2-e5ef45eff347", "@id": "/badges/replicate-numbers/", "badge_icon": "/static/img/badges/replicates-orange-circle.svg", "description": "Issues with replicate numbers"}}}]}, "validation-errors": []}