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PMID: 18369441 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

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

PLoS genetics ·Vol. 4 ·No. 3 ·2008-03-07 ·Pages e1000016

Noordermeer D, Branco MR, Splinter E, Klous P, van Ijcken W, Swagemakers S, Koutsourakis M, van der Spek P, Pombo A, de Laat W

Abstract

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.

MeSH Terms
Animals Base Sequence Chromatin/genetics DNA Primers/genetics Female Fetus/metabolism Gene Expression Regulation Gene Targeting Globins/genetics Humans In Situ Hybridization, Fluorescence Liver/metabolism Locus Control Region Mice Mice, Transgenic Multigene Family Pregnancy Transcription, Genetic
Chemicals
Chromatin DNA Primers Globins
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Noordermeer Daan
Department of Cell Biology and Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Branco Miguel R
Splinter Erik
Klous Petra
van Ijcken Wilfred
Swagemakers Sigrid
Koutsourakis Manousos
van der Spek Peter
Pombo Ana
de Laat Wouter
Conflict of Interest

The authors have declared that no competing interests exist.

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Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.1000016
Published
2008-03-07
Epub
2008-00-07
Pages
e1000016
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC2265466
Subset
IM
Grants
Medical Research Council · MC_U120061476 · United Kingdom
Databases
GEO
GSE5891
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1371/journal.pgen.1000016 PMC Full Text View journal details
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