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 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.
Noordermeer
Daan
D
Department of Cell Biology and Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
Branco
Miguel R
MR
Splinter
Erik
E
Klous
Petra
P
van Ijcken
Wilfred
W
Swagemakers
Sigrid
S
Koutsourakis
Manousos
M
van der Spek
Peter
P
Pombo
Ana
A
de Laat
Wouter
W
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
D002843:Chromatin; D017931:DNA Primers; D005914:Globins