Transcription and chromatin organization of a housekeeping gene cluster containing an integrated beta-globin locus control region.

The activity of locus control regions (LCR) has been correlated with chromatin decondensation, spreading of active chromatin marks, locus repositioning away from its chromosome territory (CT), increased association with transcription factories, and long-range interactions via chromatin looping. To i...

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Main Authors: Daan Noordermeer, Miguel R Branco, Erik Splinter, Petra Klous, Wilfred van Ijcken, Sigrid Swagemakers, Manousos Koutsourakis, Peter van der Spek, Ana Pombo, Wouter de Laat
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-03-01
Series:PLoS Genetics
Online Access:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000016&type=printable
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author Daan Noordermeer
Miguel R Branco
Erik Splinter
Petra Klous
Wilfred van Ijcken
Sigrid Swagemakers
Manousos Koutsourakis
Peter van der Spek
Ana Pombo
Wouter de Laat
author_facet Daan Noordermeer
Miguel R Branco
Erik Splinter
Petra Klous
Wilfred van Ijcken
Sigrid Swagemakers
Manousos Koutsourakis
Peter van der Spek
Ana Pombo
Wouter de Laat
author_sort Daan Noordermeer
collection DOAJ
description The activity of locus control regions (LCR) has been correlated with chromatin decondensation, spreading of active chromatin marks, locus repositioning away from its chromosome territory (CT), increased association with transcription factories, and long-range interactions via chromatin looping. To investigate the relative importance of these events in the regulation of gene expression, we targeted the human beta-globin LCR in two opposite orientations to a gene-dense region in the mouse genome containing mostly housekeeping genes. We found that each oppositely oriented LCR influenced gene expression on both sides of the integration site and over a maximum distance of 150 kilobases. A subset of genes was transcriptionally enhanced, some of which in an LCR orientation-dependent manner. The locus resides mostly at the edge of its CT and integration of the LCR in either orientation caused a more frequent positioning of the locus away from its CT. Locus association with transcription factories increased moderately, both for loci at the edge and outside of the CT. These results show that nuclear repositioning is not sufficient to increase transcription of any given gene in this region. We identified long-range interactions between the LCR and two upregulated genes and propose that LCR-gene contacts via chromatin looping determine which genes are transcriptionally enhanced.
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spelling doaj-art-3b5cfbbceb264f5f82889dbb17dcc5372025-08-20T02:17:24ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042008-03-0143e100001610.1371/journal.pgen.1000016Transcription and chromatin organization of a housekeeping gene cluster containing an integrated beta-globin locus control region.Daan NoordermeerMiguel R BrancoErik SplinterPetra KlousWilfred van IjckenSigrid SwagemakersManousos KoutsourakisPeter van der SpekAna PomboWouter de LaatThe activity of locus control regions (LCR) has been correlated with chromatin decondensation, spreading of active chromatin marks, locus repositioning away from its chromosome territory (CT), increased association with transcription factories, and long-range interactions via chromatin looping. To investigate the relative importance of these events in the regulation of gene expression, we targeted the human beta-globin LCR in two opposite orientations to a gene-dense region in the mouse genome containing mostly housekeeping genes. We found that each oppositely oriented LCR influenced gene expression on both sides of the integration site and over a maximum distance of 150 kilobases. A subset of genes was transcriptionally enhanced, some of which in an LCR orientation-dependent manner. The locus resides mostly at the edge of its CT and integration of the LCR in either orientation caused a more frequent positioning of the locus away from its CT. Locus association with transcription factories increased moderately, both for loci at the edge and outside of the CT. These results show that nuclear repositioning is not sufficient to increase transcription of any given gene in this region. We identified long-range interactions between the LCR and two upregulated genes and propose that LCR-gene contacts via chromatin looping determine which genes are transcriptionally enhanced.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000016&type=printable
spellingShingle Daan Noordermeer
Miguel R Branco
Erik Splinter
Petra Klous
Wilfred van Ijcken
Sigrid Swagemakers
Manousos Koutsourakis
Peter van der Spek
Ana Pombo
Wouter de Laat
Transcription and chromatin organization of a housekeeping gene cluster containing an integrated beta-globin locus control region.
PLoS Genetics
title Transcription and chromatin organization of a housekeeping gene cluster containing an integrated beta-globin locus control region.
title_full Transcription and chromatin organization of a housekeeping gene cluster containing an integrated beta-globin locus control region.
title_fullStr Transcription and chromatin organization of a housekeeping gene cluster containing an integrated beta-globin locus control region.
title_full_unstemmed Transcription and chromatin organization of a housekeeping gene cluster containing an integrated beta-globin locus control region.
title_short Transcription and chromatin organization of a housekeeping gene cluster containing an integrated beta-globin locus control region.
title_sort transcription and chromatin organization of a housekeeping gene cluster containing an integrated beta globin locus control region
url https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000016&type=printable
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