Biology

An atlas of open chromatin spanning diverse human cell types in health and disease
Jason Lieb, University of North Carolina at Chapel Hill

Proteins that regulate genes often bind directly to DNA, and to do so they must locally unpack the DNA. DNA is packaged into spool-like structures called nucleosomes. Nucleosome loss, or formation of “open chromatin”, is an evolutionarily conserved indicator of regulatory activity, and can be used as a molecular tag to isolate regions of the genome bound by regulatory factors. We have developed a fast, easy, and inexpensive technique called FAIRE to isolate and identify open chromatin from human cells. I will discuss FAIRE data that was obtained through a new technology called “sequencing by synthesis” or “next-gen DNA sequencing”. The data is derived from several human cell lines, human pancreatic islet cells, and from clinical breast tumor samples. We find that about 2% of the genome is open in any given cell type at about 100,000 discrete sites, but that any two human cell types share only 20-25% of these sites. Clinical breast tumors exhibit characteristic chromatin profiles that can readily distinguish tumor subtype and hormone responsiveness, with potential clinical implications. The data from pancreatic Islets is relevant to diabetes, and serves to dramatically reduce the genomic search space in the hunt for functional sequence variants that influence diabetes susceptibility.

The data to be discussed was generated by Paul Giresi, Linda Grasfeder, Kyle Gaulton, Jeremy Simon, Piotr Mieczkowski, and Takao Nammo in collaboration with Jorge Ferrer (Hospital Clinic de Barcelona), Karen Mohlke (UNC), and Charles Perou (UNC).

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Biology

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