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Lamin A, Chromatin and FPLD2: Not Just a Peripheral Ménage-à-Trois

At the nuclear periphery, the genome is anchored to A- and B-type nuclear lamins in the form of heterochromatic lamina-associated domains. A-type lamins also associate with chromatin in the nuclear interior, away from the peripheral nuclear lamina. This nucleoplasmic lamin A environment tends to be...

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Autores principales: Briand, Nolwenn, Cahyani, Inswasti, Madsen-Østerbye, Julia, Paulsen, Jonas, Rønningen, Torunn, Sørensen, Anita L., Collas, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053905/
https://www.ncbi.nlm.nih.gov/pubmed/30057899
http://dx.doi.org/10.3389/fcell.2018.00073
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author Briand, Nolwenn
Cahyani, Inswasti
Madsen-Østerbye, Julia
Paulsen, Jonas
Rønningen, Torunn
Sørensen, Anita L.
Collas, Philippe
author_facet Briand, Nolwenn
Cahyani, Inswasti
Madsen-Østerbye, Julia
Paulsen, Jonas
Rønningen, Torunn
Sørensen, Anita L.
Collas, Philippe
author_sort Briand, Nolwenn
collection PubMed
description At the nuclear periphery, the genome is anchored to A- and B-type nuclear lamins in the form of heterochromatic lamina-associated domains. A-type lamins also associate with chromatin in the nuclear interior, away from the peripheral nuclear lamina. This nucleoplasmic lamin A environment tends to be euchromatic, suggesting distinct roles of lamin A in the regulation of gene expression in peripheral and more central regions of the nucleus. The hot-spot lamin A R482W mutation causing familial partial lipodystrophy of Dunnigan-type (FPLD2), affects lamin A association with chromatin at the nuclear periphery and in the nuclear interior, and is associated with 3-dimensional (3D) rearrangements of chromatin. Here, we highlight features of nuclear lamin association with the genome at the nuclear periphery and in the nuclear interior. We address recent data showing a rewiring of such interactions in cells from FPLD2 patients, and in adipose progenitor and induced pluripotent stem cell models of FPLD2. We discuss associated epigenetic and genome conformation changes elicited by the lamin A R482W mutation at the gene level. The findings argue that the mutation adversely impacts both global and local genome architecture throughout the nucleus space. The results, together with emerging new computational modeling tools, mark the start of a new era in our understanding of the 3D genomics of laminopathies.
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spelling pubmed-60539052018-07-27 Lamin A, Chromatin and FPLD2: Not Just a Peripheral Ménage-à-Trois Briand, Nolwenn Cahyani, Inswasti Madsen-Østerbye, Julia Paulsen, Jonas Rønningen, Torunn Sørensen, Anita L. Collas, Philippe Front Cell Dev Biol Cell and Developmental Biology At the nuclear periphery, the genome is anchored to A- and B-type nuclear lamins in the form of heterochromatic lamina-associated domains. A-type lamins also associate with chromatin in the nuclear interior, away from the peripheral nuclear lamina. This nucleoplasmic lamin A environment tends to be euchromatic, suggesting distinct roles of lamin A in the regulation of gene expression in peripheral and more central regions of the nucleus. The hot-spot lamin A R482W mutation causing familial partial lipodystrophy of Dunnigan-type (FPLD2), affects lamin A association with chromatin at the nuclear periphery and in the nuclear interior, and is associated with 3-dimensional (3D) rearrangements of chromatin. Here, we highlight features of nuclear lamin association with the genome at the nuclear periphery and in the nuclear interior. We address recent data showing a rewiring of such interactions in cells from FPLD2 patients, and in adipose progenitor and induced pluripotent stem cell models of FPLD2. We discuss associated epigenetic and genome conformation changes elicited by the lamin A R482W mutation at the gene level. The findings argue that the mutation adversely impacts both global and local genome architecture throughout the nucleus space. The results, together with emerging new computational modeling tools, mark the start of a new era in our understanding of the 3D genomics of laminopathies. Frontiers Media S.A. 2018-07-09 /pmc/articles/PMC6053905/ /pubmed/30057899 http://dx.doi.org/10.3389/fcell.2018.00073 Text en Copyright © 2018 Briand, Cahyani, Madsen-Østerbye, Paulsen, Rønningen, Sørensen and Collas. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Briand, Nolwenn
Cahyani, Inswasti
Madsen-Østerbye, Julia
Paulsen, Jonas
Rønningen, Torunn
Sørensen, Anita L.
Collas, Philippe
Lamin A, Chromatin and FPLD2: Not Just a Peripheral Ménage-à-Trois
title Lamin A, Chromatin and FPLD2: Not Just a Peripheral Ménage-à-Trois
title_full Lamin A, Chromatin and FPLD2: Not Just a Peripheral Ménage-à-Trois
title_fullStr Lamin A, Chromatin and FPLD2: Not Just a Peripheral Ménage-à-Trois
title_full_unstemmed Lamin A, Chromatin and FPLD2: Not Just a Peripheral Ménage-à-Trois
title_short Lamin A, Chromatin and FPLD2: Not Just a Peripheral Ménage-à-Trois
title_sort lamin a, chromatin and fpld2: not just a peripheral ménage-à-trois
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053905/
https://www.ncbi.nlm.nih.gov/pubmed/30057899
http://dx.doi.org/10.3389/fcell.2018.00073
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