Charles E. Kaufman Foundation

2015 New Investigator Grant

Maya Capelson, Ph.D. The Nuclear Pore as a Novel Scaffold for Spatial Genome Organization

The Nuclear Pore as a Novel Scaffold for Spatial Genome Organization


All cells in an organism carry the same sequence of DNA, yet different cell types are able to express different genes from their identical DNA templates. Regulation of gene expression to turn specific genes on and off is the basis of embryonic development, during which a single cell of a fertilized egg gives rise to a multitude of highly specified cell types, each with its own expression program. The mechanisms behind how variable expression programs are set up by the cell and the organism constitute one of the largest questions in modern biology. Regulation of gene expression arises from proteins that bind to DNA and determine which genes are expressed and which are silenced. The DNA template is enclosed by the Nuclear Envelope membrane of the nucleus, separating it from the rest of the cell. This membrane is fenestrated by Nuclear Pores, which are large protein complexes that transport key molecules in and out of the nucleus. We have discovered a novel role for Nuclear Pore proteins in physically binding specific genes and conferring a particular expression state to such targets. These findings suggest a fascinating possibility that genes may be moved to and from the Nuclear Pore as a switch to turn them on and off. Based on our findings, we hypothesize that Nuclear Pores in different cell types tether different places in the genome, and that this binding plays a key role in the establishment of variable gene expression programs. We propose to systematically characterize gene sets that are bound and regulated by Nuclear Pores in different cell types, and to uncover molecular mechanisms of these interactions. Additionally, we plan to create new binding sites of the Nuclear Pore in the genome, which we will use to determine if re-positioning genes to the Nuclear Pore will turn them on or off. Ultimately, this knowledge will advance our understanding of how gene expression is regulated and has the potential to reveal a new paradigm for directing gene activity.

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