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Cell-type specialization is encoded by specific chromatin topologies

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Item Type:Article
Title:Cell-type specialization is encoded by specific chromatin topologies
Creators Name:Winick-Ng, W. and Kukalev, A. and Harabula, I. and Zea-Redondo, L. and Szabó, D. and Meijer, M. and Serebreni, L. and Zhang, Y. and Bianco, S. and Chiariello, A.M. and Irastorza-Azcarate, I. and Thieme, C.J. and Sparks, T.M. and Carvalho, S. and Fiorillo, L. and Musella, F. and Irani, E. and Triglia, E.T. and Kolodziejczyk, A.A. and Abentung, A. and Apostolova, G. and Paul, E.J. and Franke, V. and Kempfer, R. and Akalin, A. and Teichmann, S.A. and Dechant, G. and Ungless, M.A. and Nicodemi, M. and Welch, L. and Castelo-Branco, G. and Pombo, A.
Abstract:The three-dimensional (3D) structure of chromatin is intrinsically associated with gene regulation and cell function. 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. However, changes in chromatin organization captured by imaging, such as the relocation of Bdnf away from the nuclear periphery after activation, are invisible with such approaches. Here we developed immunoGAM, an extension of genome architecture mapping (GAM), 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. 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.
Keywords:Animals, Mice
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group
Date:17 November 2021
Official Publication:https://doi.org/10.1038/s41586-021-04081-2
PubMed:View item in PubMed
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https://edoc.mdc-berlin.de/18939/Preprint version

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