Genome Architecture Mapping: discovering chromatin contacts in rare cell types
Ponente: Ana Pombo
Max Delbruck Center for Molecular Medicine [Berlin, Germany]
Host: Mercedes Dosil
Salón de Actos del Centro de Investigación del Cáncer
The folding of chromosomes and the structural organization of the genome impacts human health and disease. Gene expression is controlled by long-range chromatin contacts between non-coding regulatory regions and their target genes. Disruption of chromatin contacts due to disease-associated structural changes in the linear genome can result in altered patterns of gene expression. However, it remains challenging to determine 3D chromosome topologies in specific cells types especially in complex tissues, such as specific neurons in the brain.
To study the relationship between 3D genome folding and gene expression, we have developed Genome Architecture Mapping (GAM), a novel ligation-free technique, which overcomes limitations of current 3C-based approaches. GAM extracts spatial information by sequencing DNA from a large collection of thin nuclear sections, before quantifying the frequency of locus co-segregation across the collection of sections. By applying GAM to mouse embryonic stem cells, we have previously identified specific chromatin contacts enriched for interactions between active genes and enhancers spanning large genomic distances. We currently apply GAM in neuronal subtypes directly microdissected from mouse brain. Our work shows that genome architecture is highly dependent on cell-type specific gene expression patterns at both short and long genomic distances, with implications to our understanding of genetic variation and disease.