Description:

The Department of Biochemistry and Molecular Genetics Departmental Seminar Series presents:

Denes Hnisz, PhD
Postdoctoral Fellow
Whitehead Institute for Biomedical Research, MA

New insights into gene control have emerged from studying mammalian chromosome structures. We have constructed first-generation maps of chromosome structures in human cells by identifying transcriptional enhancers and insulators and placing them within the context of cohesin-associated CTCF-CTCF DNA loops using ChIA-PET data. The CTCF- CTCF loops form a chromosomal framework of insulated neighborhoods, which in turn form topologically associated domains (TADs). Some of these CTCF-CTCF loops are preserved during development and differentiation. Regulatory changes in enhancer- promoter interactions occur within insulated neighborhoods during cell state transitions. The CTCF loop anchor regions are conserved across species, influence gene expression, and are frequent sites of mutations in cancer cells, underscoring their functional importance in cellular regulation. These 3D regulatory maps of human pluripotent cells therefore provide a foundation for future interrogation of the relationships between chromosome structure and gene control in development and disease.