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The 3D nuclear conformation of the major histocompatibility complex changes upon cell activation both in porcine and human macrophages

BACKGROUND: The crucial role of the major histocompatibility complex (MHC) for the immune response to infectious diseases is well-known, but no information is available on the 3D nuclear organization of this gene-dense region in immune cells, whereas nuclear architecture is known to play an essentia...

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Autores principales: Mompart, Florence, Kamgoué, Alain, Lahbib-Mansais, Yvette, Robelin, David, Bonnet, Agnès, Rogel-Gaillard, Claire, Kocanova, Silvia, Yerle-Bouissou, Martine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442435/
https://www.ncbi.nlm.nih.gov/pubmed/34521351
http://dx.doi.org/10.1186/s12860-021-00384-4
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author Mompart, Florence
Kamgoué, Alain
Lahbib-Mansais, Yvette
Robelin, David
Bonnet, Agnès
Rogel-Gaillard, Claire
Kocanova, Silvia
Yerle-Bouissou, Martine
author_facet Mompart, Florence
Kamgoué, Alain
Lahbib-Mansais, Yvette
Robelin, David
Bonnet, Agnès
Rogel-Gaillard, Claire
Kocanova, Silvia
Yerle-Bouissou, Martine
author_sort Mompart, Florence
collection PubMed
description BACKGROUND: The crucial role of the major histocompatibility complex (MHC) for the immune response to infectious diseases is well-known, but no information is available on the 3D nuclear organization of this gene-dense region in immune cells, whereas nuclear architecture is known to play an essential role on genome function regulation. We analyzed the spatial arrangement of the three MHC regions (class I, III and II) in macrophages using 3D-FISH. Since this complex presents major differences in humans and pigs with, notably, the presence of the centromere between class III and class II regions in pigs, the analysis was implemented in both species to determine the impact of this organization on the 3D conformation of the MHC. The expression level of the three genes selected to represent each MHC region was assessed by quantitative real-time PCR. Resting and lipopolysaccharide (LPS)-activated states were investigated to ascertain whether a response to a pathogen modifies their expression level and their 3D organization. RESULTS: While the three MHC regions occupy an intermediate radial position in porcine macrophages, the class I region was clearly more peripheral in humans. The BAC center-to-center distances allowed us to propose a 3D nuclear organization of the MHC in each species. LPS/IFNγ activation induces a significant decompaction of the chromatin between class I and class III regions in pigs and between class I and class II regions in humans. We detected a strong overexpression of TNFα (class III region) in both species. Moreover, a single nucleus analysis revealed that the two alleles can have either the same or a different compaction pattern. In addition, macrophage activation leads to an increase in alleles that present a decompacted pattern in humans and pigs. CONCLUSIONS: The data presented demonstrate that: (i) the MHC harbors a different 3D organization in humans and pigs; (ii) LPS/IFNγ activation induces chromatin decompaction, but it is not the same area affected in the two species. These findings were supported by the application of an original computation method based on the geometrical distribution of the three target genes. Finally, the position of the centromere inside the swine MHC could influence chromatin reorganization during the activation process. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12860-021-00384-4.
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spelling pubmed-84424352021-09-15 The 3D nuclear conformation of the major histocompatibility complex changes upon cell activation both in porcine and human macrophages Mompart, Florence Kamgoué, Alain Lahbib-Mansais, Yvette Robelin, David Bonnet, Agnès Rogel-Gaillard, Claire Kocanova, Silvia Yerle-Bouissou, Martine BMC Mol Cell Biol Research BACKGROUND: The crucial role of the major histocompatibility complex (MHC) for the immune response to infectious diseases is well-known, but no information is available on the 3D nuclear organization of this gene-dense region in immune cells, whereas nuclear architecture is known to play an essential role on genome function regulation. We analyzed the spatial arrangement of the three MHC regions (class I, III and II) in macrophages using 3D-FISH. Since this complex presents major differences in humans and pigs with, notably, the presence of the centromere between class III and class II regions in pigs, the analysis was implemented in both species to determine the impact of this organization on the 3D conformation of the MHC. The expression level of the three genes selected to represent each MHC region was assessed by quantitative real-time PCR. Resting and lipopolysaccharide (LPS)-activated states were investigated to ascertain whether a response to a pathogen modifies their expression level and their 3D organization. RESULTS: While the three MHC regions occupy an intermediate radial position in porcine macrophages, the class I region was clearly more peripheral in humans. The BAC center-to-center distances allowed us to propose a 3D nuclear organization of the MHC in each species. LPS/IFNγ activation induces a significant decompaction of the chromatin between class I and class III regions in pigs and between class I and class II regions in humans. We detected a strong overexpression of TNFα (class III region) in both species. Moreover, a single nucleus analysis revealed that the two alleles can have either the same or a different compaction pattern. In addition, macrophage activation leads to an increase in alleles that present a decompacted pattern in humans and pigs. CONCLUSIONS: The data presented demonstrate that: (i) the MHC harbors a different 3D organization in humans and pigs; (ii) LPS/IFNγ activation induces chromatin decompaction, but it is not the same area affected in the two species. These findings were supported by the application of an original computation method based on the geometrical distribution of the three target genes. Finally, the position of the centromere inside the swine MHC could influence chromatin reorganization during the activation process. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12860-021-00384-4. BioMed Central 2021-09-14 /pmc/articles/PMC8442435/ /pubmed/34521351 http://dx.doi.org/10.1186/s12860-021-00384-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Mompart, Florence
Kamgoué, Alain
Lahbib-Mansais, Yvette
Robelin, David
Bonnet, Agnès
Rogel-Gaillard, Claire
Kocanova, Silvia
Yerle-Bouissou, Martine
The 3D nuclear conformation of the major histocompatibility complex changes upon cell activation both in porcine and human macrophages
title The 3D nuclear conformation of the major histocompatibility complex changes upon cell activation both in porcine and human macrophages
title_full The 3D nuclear conformation of the major histocompatibility complex changes upon cell activation both in porcine and human macrophages
title_fullStr The 3D nuclear conformation of the major histocompatibility complex changes upon cell activation both in porcine and human macrophages
title_full_unstemmed The 3D nuclear conformation of the major histocompatibility complex changes upon cell activation both in porcine and human macrophages
title_short The 3D nuclear conformation of the major histocompatibility complex changes upon cell activation both in porcine and human macrophages
title_sort 3d nuclear conformation of the major histocompatibility complex changes upon cell activation both in porcine and human macrophages
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442435/
https://www.ncbi.nlm.nih.gov/pubmed/34521351
http://dx.doi.org/10.1186/s12860-021-00384-4
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