PT  - JOURNAL ARTICLE
AU  - Muller Héloïse
AU  - Scolari F. Vittore
AU  - Mercy Guillaume
AU  - Agier Nicolas
AU  - Aurèle Piazza
AU  - Lazar-Stefanita Luciana
AU  - Descorps-Declere Stephane
AU  - Espeli Olivier
AU  - Llorente Bertrand
AU  - Fischer Gilles
AU  - Mozziconacci Julien
AU  - Koszul Romain
TI  - Redesigning chromosomes for optimized Hi-C assay provides insights on loop formation and homologs pairing during meiosis
AID  - 10.1101/169847
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 169847
4099  - http://biorxiv.org/content/early/2017/12/29/169847.short
4100  - http://biorxiv.org/content/early/2017/12/29/169847.full
AB  - In all chromosome conformation capture based experiments the accuracy with which contacts are detected varies considerably because of the uneven distribution of restriction sites along genomes. In addition, repeated sequences as well as homologous, large identical regions remain invisible to the assay because of the ambiguities they introduce during the alignment of the sequencing reads along the genome. As a result, the investigation of homologs during meiosis prophase through 3C studies has been limited. Here, we redesigned and reassembled in yeast a 145kb region with regularly spaced restriction sites for various enzymes. Thanks to this Syn-3C design, we enhanced the signal to noise ratio and improved the visibility of the entire region. We also improved our understanding of Hi-C data and definition of resolution. The redesigned sequence is now distinguishable from its native homologous counterpart in an isogenic diploid strain. As a proof of principle, we track the establishment of homolog pairing during meiotic prophase in a synchronized population. This provides new insights on the individualization and pairing of homologs, as well as on their internal restructuration into arrays of loops during meiosis prophase. Overall, we show the interest of redesigned genomic regions to explore complex biological questions otherwise difficult to address.