Modulated contact frequencies at gene-rich loci support a statistical helix model for mammalian chromatin organization

ABSTRACT: BACKGROUND: Despite its critical role for mammalian gene regulation, the basic structural landscape of chromatin in living cells remains largely unknown within chromosomal territories below the megabase scale. RESULTS: Here, using the 3C-qPCR method, we investigate contact frequencies at high resolution within interphase chromatin at several mouse loci. We find that, at several gene-rich loci, contact frequencies undergo a periodical modulation (every 90 to 100 kb) that affects chromatin dynamics over large genomic distances (a few hundred kilobases). Interestingly, this modulation appears to be conserved in human cells, and bioinformatic analyses of locus-specific, long-range cis-interactions suggest that it may underlie the dynamics of a significant number of gene-rich domains in mammals, thus contributing to genome evolution. Finally, using an original model derived from polymer physics, we show that this modulation can be understood as a fundamental helix shape that chromatin tends to adopt in gene-rich domains when no significant locus-specific interaction takes place. CONCLUSIONS: Altogether, our work unveils a fundamental aspect of chromatin dynamics in mammals and contributes to a better understanding of genome organization within chromosomal territories.