Cell-type specialization is encoded by specific chromatin topologies.
Warren Winick-Ng,Alexander Kukalev,Izabela Harabula,Izabela Harabula,Luna Zea-Redondo,Luna Zea-Redondo,Dominik Szabo,Dominik Szabo,Mandy Meijer,Leonid Serebreni,Leonid Serebreni,Yingnan Zhang,Simona Bianco,Andrea M. Chiariello,Ibai Irastorza-Azcarate,Christoph J. Thieme,Thomas M Sparks,Sílvia Carvalho,Luca Fiorillo,Francesco Musella,Ehsan Irani,Elena Torlai Triglia,Elena Torlai Triglia,Aleksandra A. Kolodziejczyk,Aleksandra A. Kolodziejczyk,Aleksandra A. Kolodziejczyk,Andreas Abentung,Andreas Abentung,Galina Apostolova,Eleanor J. Paul,Eleanor J. Paul,Vedran Franke,Rieke Kempfer,Rieke Kempfer,Altuna Akalin,Sarah A. Teichmann,Sarah A. Teichmann,Georg Dechant,Mark A. Ungless,Mario Nicodemi,Lonnie R. Welch,Gonçalo Castelo-Branco,Ana Pombo,Ana Pombo +43 more
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TLDR
In this article, an extension of genome architecture mapping (GAM) was developed to map 3D chromatin topology genome-wide in specific brain cell types, without tissue disruption, from single animals.Abstract:
The three-dimensional (3D) structure of chromatin is intrinsically associated with gene regulation and cell function1–3. 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 hippocampi4–6. However, changes in chromatin organization captured by imaging, such as the relocation of Bdnf away from the nuclear periphery after activation7, are invisible with such approaches8. 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 dissociation2,10. 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. A new technique called immunoGAM, which combines genome architecture mapping (GAM) with immunoselection, enabled the discovery of specialized chromatin conformations linked to gene expression in specific cell populations from mouse brain tissues.read more
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The spatial organization of transcriptional control
TL;DR: New tools for high-throughput super-resolution imaging of chromatin have directly visualized the 3D chromatin organization, settling some debates left unresolved by earlier indirect methods, challenging some earlier models of regulatory specificity and creating hypotheses about the role of Chromatin structure in transcriptional regulation.
Journal ArticleDOI
Regulating specificity in enhancer-promoter communication.
TL;DR: A review of the mechanisms by which enhancers engage with promoters, including recent findings on the role of cohesin and the Mediator complex, and how this specificity in enhancer-promoter communication is encoded is provided in this article .
Journal ArticleDOI
Normal and Pathological NRF2 Signalling in the Central Nervous System
Tony Heurtaux,David Bouvier,Alexandre Benani,Sergio Helgueta Romero,Katrin Frauenknecht,Michel Mittelbronn,Lasse Sinkkonen +6 more
TL;DR: Recent data is gathered about the contribution of the NRF2 pathway in the healthy brain as well as during metabolic diseases, cancer, ageing, and ageing-related neurodegenerative diseases, and the need for better understanding of cell-type-specific functions ofNRF2 in these different fields is discussed.
Journal ArticleDOI
Nuclear speckles - a driving force in gene expression.
TL;DR: As discussed in this Review, nuclear speckles represent a fascinating target of study not only to reveal the links between gene positioning, genome subcompartments and gene activity, but also as a potential target for therapeutics.
Journal ArticleDOI
A noncoding single-nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation
Connor Yanchus,Kristen L. Drucker,Thomas M. Kollmeyer,Ricky Tsai,Mi Liang,L. Jiang,Judy Pawling,A. Ali,Patrice Decker,Matthew L. Kosel,Abhinash Panda,Ahmad Malik,Khaloud Al-Zahrani,Joseph Hernandez,Mehvish Naseer Ahmed,Sankaran Loganathan,Dan Trcka,Antony L Michaelraj,Jessyka Fortin,Parisa Mazrooei,L Zhou,Avraam Elia,Mathieu Lupien,H O He,L. Wang,Alexej Abyzov,Joe Dennis,Matthew Wilson,Jeff Wrana,Daniel H. Lachance,Margaret Wrensch,J. Wienck,Len A. Pennacchio,Diane E. Dickel,Axel Visel,M R Taylor,Gelareh Zadeh,P. Dirks,Jeanette E. Eckel Passow,Tony Mak,Evgeny Z. Kvon,R. Jenkins,Daniel Schramek +42 more
TL;DR: It is revealed that the single nucleotide polymorphism rs55705857 itself is the causal variant and is associated with molecular pathways that drive LGG, and mechanisms of the heritable predisposition to lethal glioma in ~40% of LGG-patients are revealed.
References
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