April 6, 2016 | 4:00 p.m. - 5:30 p.m.

Ana Pombo, DPhilMax Delbruck Center for Molecular Medicine

Complex multi-enhancer contacts captured in ES cells by

Genome Architecture Mapping (GAM)

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Ana Pombo received her DPhil in 1998, from University of Oxford, UK. In 1998, she was awarded the Royal Society Dorothy Hodgkin Fellowship (Royal Society) and in 2000, she was appointed Senior Lecturer at Imperial College London, and started her independent research group at the MRC Clinical Sciences Centre, London, UK, working on gene expression and genome architecture.

In 2007, she was promoted to Reader in Cell Biology, and was awarded the Robert Feulgen Prize for her contributions to imaging nuclear architecture. Ana was promoted to Professor in Cell Biology (Imperial College London) in 2011, and appointed Chair of the Integrative Biology section of the MRC Clinical Sciences Centre in 2012.

Her laboratory moved to Berlin Institute for Medical Systems Biology, MDC, Berlin, Germany, in 2013, and she was appointed as Professor (W3) at Humboldt University in Berlin. She studies the mechanisms that control gene priming prior to activation in ES and differentiated cells, and how the three-dimensional folding of chromatin influences gene expression in development and disease.

The organization of the genome in the nucleus and the interactions of genes with their regulatory elements are key features of transcriptional control and their disruption causes disease. Technologies based on chromosome conformation capture (3C) have profoundly expanded our understanding of the role of genome architecture in gene regulation. We introduce Genome Architecture Mapping (GAM), a novel genome-wide method for measuring three-dimensional chromatin topology.

Exploration of the most prominent chromatin contacts detected in mouse ES cells using GAM identifies most specific chromatin contacts between active genes and enhancers across very large genomic distances. GAM also reveals abundant three-way contacts genome-wide, especially between the enhancers most highly occupied by pluripotency transcription factors and highly transcribed genomic regions.

Our results highlight a previously inaccessible complexity in genome architecture and a major role for gene-expression specific contacts in organizing genome architecture of mammalian nuclei.