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β-Globin cis-elements determine differential nuclear targeting through epigenetic modifications

Increasing evidence points to nuclear compartmentalization as a contributing mechanism for gene regulation, yet mechanisms for compartmentalization remain unclear. In this paper, we use autonomous targeting of bacterial artificial chromosome (BAC) transgenes to reveal cis requirements for peripheral...

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Detalles Bibliográficos
Autores principales: Bian, Qian, Khanna, Nimish, Alvikas, Jurgis, Belmont, Andrew S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857487/
https://www.ncbi.nlm.nih.gov/pubmed/24297746
http://dx.doi.org/10.1083/jcb.201305027
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author Bian, Qian
Khanna, Nimish
Alvikas, Jurgis
Belmont, Andrew S.
author_facet Bian, Qian
Khanna, Nimish
Alvikas, Jurgis
Belmont, Andrew S.
author_sort Bian, Qian
collection PubMed
description Increasing evidence points to nuclear compartmentalization as a contributing mechanism for gene regulation, yet mechanisms for compartmentalization remain unclear. In this paper, we use autonomous targeting of bacterial artificial chromosome (BAC) transgenes to reveal cis requirements for peripheral targeting. Three peripheral targeting regions (PTRs) within an HBB BAC bias a competition between pericentric versus peripheral heterochromatin targeting toward the nuclear periphery, which correlates with increased H3K9me3 across the β-globin gene cluster and locus control region. Targeting to both heterochromatin compartments is dependent on Suv39H-mediated H3K9me3 methylation. In different chromosomal contexts, PTRs confer no targeting, targeting to pericentric heterochromatin, or targeting to the periphery. A combination of fluorescent in situ hybridization, BAC transgenesis, and knockdown experiments reveals that peripheral tethering of the endogenous HBB locus depends both on Suv39H-mediated H3K9me3 methylation over hundreds of kilobases surrounding HBB and on G9a-mediated H3K9me2 methylation over flanking sequences in an adjacent lamin-associated domain. Our results demonstrate that multiple cis-elements regulate the overall balance of specific epigenetic marks and peripheral gene targeting.
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spelling pubmed-38574872014-06-09 β-Globin cis-elements determine differential nuclear targeting through epigenetic modifications Bian, Qian Khanna, Nimish Alvikas, Jurgis Belmont, Andrew S. J Cell Biol Research Articles Increasing evidence points to nuclear compartmentalization as a contributing mechanism for gene regulation, yet mechanisms for compartmentalization remain unclear. In this paper, we use autonomous targeting of bacterial artificial chromosome (BAC) transgenes to reveal cis requirements for peripheral targeting. Three peripheral targeting regions (PTRs) within an HBB BAC bias a competition between pericentric versus peripheral heterochromatin targeting toward the nuclear periphery, which correlates with increased H3K9me3 across the β-globin gene cluster and locus control region. Targeting to both heterochromatin compartments is dependent on Suv39H-mediated H3K9me3 methylation. In different chromosomal contexts, PTRs confer no targeting, targeting to pericentric heterochromatin, or targeting to the periphery. A combination of fluorescent in situ hybridization, BAC transgenesis, and knockdown experiments reveals that peripheral tethering of the endogenous HBB locus depends both on Suv39H-mediated H3K9me3 methylation over hundreds of kilobases surrounding HBB and on G9a-mediated H3K9me2 methylation over flanking sequences in an adjacent lamin-associated domain. Our results demonstrate that multiple cis-elements regulate the overall balance of specific epigenetic marks and peripheral gene targeting. The Rockefeller University Press 2013-12-09 /pmc/articles/PMC3857487/ /pubmed/24297746 http://dx.doi.org/10.1083/jcb.201305027 Text en © 2013 Bian et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Bian, Qian
Khanna, Nimish
Alvikas, Jurgis
Belmont, Andrew S.
β-Globin cis-elements determine differential nuclear targeting through epigenetic modifications
title β-Globin cis-elements determine differential nuclear targeting through epigenetic modifications
title_full β-Globin cis-elements determine differential nuclear targeting through epigenetic modifications
title_fullStr β-Globin cis-elements determine differential nuclear targeting through epigenetic modifications
title_full_unstemmed β-Globin cis-elements determine differential nuclear targeting through epigenetic modifications
title_short β-Globin cis-elements determine differential nuclear targeting through epigenetic modifications
title_sort β-globin cis-elements determine differential nuclear targeting through epigenetic modifications
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857487/
https://www.ncbi.nlm.nih.gov/pubmed/24297746
http://dx.doi.org/10.1083/jcb.201305027
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