Zusammenfassung
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 three-dimensional folding of a 1 Mbp region of human
chromosome 11 containing the beta-globin genes by integrating looping
interactions of the CCCTC-binding 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. In
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 position 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.
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