In the last decade, great progress in our understanding of the spatial organization of the genome was achieved with the explosion of chromosome conformation capture technologies (from 3C to Hi-C).
Chromosomes are partitioned into units that occupy distinct compartments according to the temporal order of replication (replication timing – RT). On a large scale, chromosomes are separated into active (“A”) or inactive (“B”) compartments defined by principal component analysis of Hi-C data. At the sub-megabase scale, chromosomes are folded into self-interacting topologically associating domains (TADs).
3D genome organization modulates distinct nuclear processes and is coordinated with RT and nuclear lamina association. In fact, A/B compartments align with early and late replication, respectively and TADs align with the replication domains. Late RDs are also associated with the nuclear periphery and correspond to the lamin-associated domains (LADs).
RT and A/B compartmentalization are highly conserved and alterations in RT and 3D organization are associated with many diseases, underscoring the importance of genome architecture in gene function regulation.
Genome-wide analysis of nuclear architecture and function
Genomic technologies based on next-generation sequencing (NGS) allow the characterization of nuclear organization and function.
In the Rivera-Mulia lab, we perform genome-wide analyses of the temporal order of DNA replication (Repli-seq), 3D genome architecture (Hi-C), gene expression (RNA-seq) and chromatin accessibility to identify regulatory mechanisms of nuclear organization.
