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Lamin A/C-promoter interactions specify chromatin state–dependent transcription outcomes
The nuclear lamina is implicated in the organization of the eukaryotic nucleus. Association of nuclear lamins with the genome occurs through large chromatin domains including mostly, but not exclusively, repressed genes. How lamin interactions with regulatory elements modulate gene expression in dif...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3787256/ https://www.ncbi.nlm.nih.gov/pubmed/23861385 http://dx.doi.org/10.1101/gr.159400.113 |
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author | Lund, Eivind Oldenburg, Anja R. Delbarre, Erwan Freberg, Christel T. Duband-Goulet, Isabelle Eskeland, Ragnhild Buendia, Brigitte Collas, Philippe |
author_facet | Lund, Eivind Oldenburg, Anja R. Delbarre, Erwan Freberg, Christel T. Duband-Goulet, Isabelle Eskeland, Ragnhild Buendia, Brigitte Collas, Philippe |
author_sort | Lund, Eivind |
collection | PubMed |
description | The nuclear lamina is implicated in the organization of the eukaryotic nucleus. Association of nuclear lamins with the genome occurs through large chromatin domains including mostly, but not exclusively, repressed genes. How lamin interactions with regulatory elements modulate gene expression in different cellular contexts is unknown. We show here that in human adipose tissue stem cells, lamin A/C interacts with distinct spatially restricted subpromoter regions, both within and outside peripheral and intra-nuclear lamin-rich domains. These localized interactions are associated with distinct transcriptional outcomes in a manner dependent on local chromatin modifications. Down-regulation of lamin A/C leads to dissociation of lamin A/C from promoters and remodels repressive and permissive histone modifications by enhancing transcriptional permissiveness, but is not sufficient to elicit gene activation. Adipogenic differentiation resets a large number of lamin-genome associations globally and at subpromoter levels and redefines associated transcription outputs. We propose that lamin A/C acts as a modulator of local gene expression outcome through interaction with adjustable sites on promoters, and that these position-dependent transcriptional readouts may be reset upon differentiation. |
format | Online Article Text |
id | pubmed-3787256 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-37872562014-04-01 Lamin A/C-promoter interactions specify chromatin state–dependent transcription outcomes Lund, Eivind Oldenburg, Anja R. Delbarre, Erwan Freberg, Christel T. Duband-Goulet, Isabelle Eskeland, Ragnhild Buendia, Brigitte Collas, Philippe Genome Res Research The nuclear lamina is implicated in the organization of the eukaryotic nucleus. Association of nuclear lamins with the genome occurs through large chromatin domains including mostly, but not exclusively, repressed genes. How lamin interactions with regulatory elements modulate gene expression in different cellular contexts is unknown. We show here that in human adipose tissue stem cells, lamin A/C interacts with distinct spatially restricted subpromoter regions, both within and outside peripheral and intra-nuclear lamin-rich domains. These localized interactions are associated with distinct transcriptional outcomes in a manner dependent on local chromatin modifications. Down-regulation of lamin A/C leads to dissociation of lamin A/C from promoters and remodels repressive and permissive histone modifications by enhancing transcriptional permissiveness, but is not sufficient to elicit gene activation. Adipogenic differentiation resets a large number of lamin-genome associations globally and at subpromoter levels and redefines associated transcription outputs. We propose that lamin A/C acts as a modulator of local gene expression outcome through interaction with adjustable sites on promoters, and that these position-dependent transcriptional readouts may be reset upon differentiation. Cold Spring Harbor Laboratory Press 2013-10 /pmc/articles/PMC3787256/ /pubmed/23861385 http://dx.doi.org/10.1101/gr.159400.113 Text en © 2013, Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/. |
spellingShingle | Research Lund, Eivind Oldenburg, Anja R. Delbarre, Erwan Freberg, Christel T. Duband-Goulet, Isabelle Eskeland, Ragnhild Buendia, Brigitte Collas, Philippe Lamin A/C-promoter interactions specify chromatin state–dependent transcription outcomes |
title | Lamin A/C-promoter interactions specify chromatin state–dependent transcription outcomes |
title_full | Lamin A/C-promoter interactions specify chromatin state–dependent transcription outcomes |
title_fullStr | Lamin A/C-promoter interactions specify chromatin state–dependent transcription outcomes |
title_full_unstemmed | Lamin A/C-promoter interactions specify chromatin state–dependent transcription outcomes |
title_short | Lamin A/C-promoter interactions specify chromatin state–dependent transcription outcomes |
title_sort | lamin a/c-promoter interactions specify chromatin state–dependent transcription outcomes |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3787256/ https://www.ncbi.nlm.nih.gov/pubmed/23861385 http://dx.doi.org/10.1101/gr.159400.113 |
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