title: Transcription and chromatin organization of a housekeeping gene cluster containing an integrated beta-globin locus control region.
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.
authors: Department of Cell Biology and Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors: Daan
authors: D
authors: Noordermeer
authors: Miguel R
authors: MR
authors: Branco
authors: Erik
authors: E
authors: Splinter
authors: Petra
authors: P
authors: Klous
authors: Wilfred
authors: W
authors: van Ijcken
authors: Sigrid
authors: S
authors: Swagemakers
authors: Manousos
authors: M
authors: Koutsourakis
authors: Peter
authors: P
authors: van der Spek
authors: Ana
authors: A
authors: Pombo
authors: Wouter
authors: W
authors: de Laat
mesh_terms: D000818:Animals; D001483:Base Sequence; D002843:Chromatin / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005333:Fetus / Q000378:metabolism; D005786:Gene Expression Regulation; D018390:Gene Targeting; D005914:Globins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008099:Liver / Q000378:metabolism; D019901:Locus Control Region; D051379:Mice; D008822:Mice, Transgenic; D005810:Multigene Family; D011247:Pregnancy; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D017931:DNA Primers; D005914:Globins