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"Poised transcription at Polycomb repressed genes: lessons from neuronal and cardiac differentiation"

"Poised transcription at Polycomb repressed genes: lessons from neuronal and cardiac differentiation"

Event Date
24 May 2018 - 12:00 to 13:00
Location
CRM Seminar Room
Speaker Name
Prof. Ana Pombo
Speaker Organisation
Berlin Institute for Medical Systems Biology Max-Delbrück-Centrum für Molekulare Medizin
Host

Biosketch

 

Ana Pombo investigates how the 3D folding of chromosomes influences gene expression in mammalian development and disease, and epigenetic mechanisms that prime genes for future activation. She received her DPhil from University of Oxford (1998, UK) where she identified transcription factories in mammalian nuclei. She was awarded a Royal Society Dorothy Hodgkin Fellowship (UK; 1998-2002), and started leading her research group in 2000 at the MRC London Institute for Medical Sciences, Imperial College London (UK). Her laboratory moved to the Berlin Institute for Medical Systems Biology, at the Max Delbrueck Center (Berlin, Germany) in 2013, and she was appointed Professor (W3) at Humboldt University of Berlin.

 

In 2006, Her lab showed that human chromosomes intermingle with each other, promoting specific patterns of chromosomal translocations. In 2007, they were the first to identify unusual poised RNA polymerase II complexes at genes regulated by Polycomb repressor complexes, which are epigenetic enzymes essential for cell lineage commitment. More recently, they have shown that poised pol II co-associates at Polycomb-repressed genes from ESCs to terminally differentiated neurons. She has also shown the importance of long-range genomic contacts between active genes and poised genes in mouse embryonic stem cells, by combining epigenomics, physics modelling and high-resolution imaging to. She has developed Genome Architecture Mapping (GAM), an exquisite technology to map the 3D structure of chromosomes genome-wide which has unique advantages. Using GAM, her lab showed that active genes and enhancers form the most specific chromatin contacts, including previously unappreciated complex three-way contacts between super-enhancers, which span the length of whole chromosomes. GAM is uniquely powerful to quantify the higher-order complexity of 3D genome and the study of rare cell types directly from tissue, avoiding dissociation, including from precious human biopsies. These developments open a huge field of potential applications to identify the genes affected by disease-associated genetic variants present in non-coding parts of the genome, through long-range chromatin contacts.