SciLifeLab The Svedberg seminar series 2014-03-24
Ludwig Institute for Cancer Research and University of California, San Diego School of Medicine, US
Dr. Bing Ren’s research is focused on genomic and epigenomic analyses of human embryonic stem cell differentiation and mammalian development. Bing completed his PhD at Harvard University at Tom Maniatis’s lab studying transcriptional regulation. He then moved to the Whitehead Institute for Biomedical Research/MIT at Richard Young’s lab where, as postdoc, he developed the first chromatin immunoprecipitation-microarray (ChIP-chip) technique, one of the main genomic approaches for studying in vivo transcription factor binding and chromatin modification states. He then started his own lab at the Ludwig Institute for Cancer Research-San Diego. The Ren lab has contributed to the annotation of transcriptional regulatory sequences in the human and mouse genomes, characterization of epigenomes of the human cell types, and understanding of the chromatin architecture in mammalian cells. Bing has been a participant of the ENCODE consortium since 2003, and a member of the NIH Roadmap Epigenomic Project since 2008.
Long-range Control of Gene Regulation in Health and Diseases
A major challenge confronting the biomedical research field is to elucidate how genome sequence directs temporal and tissue specific gene expression programs during development. A large number of potential cis regulatory sequences have been annotated in the human genome, thanks to advances in high throughout technologies, but the function of these elements and their roles in health and diseases remain largely uncharacterized. In this presentation I will discuss results from experiments designed to understand the gene regulatory programs controlling ES cell differentiation. We have used high throughput approaches to characterize the transcriptome, DNA methylation, chromatin modification and higher order chromatin structure in human embryonic stem cells (hESC) as they differentiate into four distinct embryonic cell lineages. Integrative analysis of these datasets revealed widespread remodeling of the epigenome and extensive reorganization of higher-order chromatin structure during hESC differentiation. The topological domains remain largely intact but inter-domain association patterns change dramatically, coincident with widespread changes in chromatin state and gene expression. More over, pervasive allelic gene activities are detected in each lineage, after the complete haplotypes of these hESC were resolved by analyzing the chromatin interaction maps using a novel computational algorithm. The allelic gene expression patterns can be correlated to epigenetic state at distal enhancers, supporting the role of these elements in regulating gene expression over a distance.
Host: Aristidis Moustakas