Genome-wide Chromatin Maps Derived from Limited Numbers of Hematopoietic Progenitors

Whole genome mapping of protein-DNA interactions can be performed by coupling chromatin immunoprecipitation (ChIP) with high-throughput sequencing (ChIP-Seq). However, current methods require large amounts of starting materials which precludes their application to rare cell types. Here, we combine a high-sensitivity ChIP assay with a novel library preparation procedure to map histone modifications in as few as 10,000 cells. We apply the technique to acquire genome-wide chromatin maps for an enriched population of hematopoietic progenitors, and thereby gain insight into their developmental program. Overall design: An optimized ChIP protocol for small number of cells and a novel Librray preperation methods for high throughput sequencing of picograms amount of ChIP DNA.