The principles underlying the architectural landscape of chromatin beyond the
nucleosome level in living cells remains largely unknown despite its potential
to play a role in mammalian gene regulation. We investigated the 3-dimensional
folding of a 1 Mbp region of human chromosome 11 containing the {\beta}-globin
genes by integrating looping interactions of the insulator protein CTCF
determined comprehensively by chromosome conformation capture (3C) into a
polymer model of chromatin. We find that CTCF-mediated cell type specific
interactions in erythroid cells are organized to favor contacts known to occur
in vivo between the {\beta}-globin locus control region (LCR) and genes. In
these cells, the modeled {\beta}-globin domain folds into a globule with the
LCR and the active globin genes on the periphery. By contrast, in non-erythroid
cells, the globule is less compact with few but dominant CTCF interactions
driving the genes away from the LCR. This leads to a decrease in contact
frequencies that can exceed 1000-fold depending on the stiffness of the
chromatin and the exact positioning of the genes. Our findings show that an
ensemble of CTCF contacts functionally affects spatial distances between
control elements and target genes contributing to chromosomal organization
required for transcription.Comment: Full article, including Supp. Mat., is available at Nucleic Acids
Research, doi: 10.1093/nar/gks53
