Genome-wide chromatin maps derived from limited numbers of hematopoietic progenitors

Improving the protocols for chromatin immunoprecipitation and library construction for the Illumina Genome Analyzer allows for chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) experiments on input samples as small as 10,000 cells and yields information on bivalent chromatin domains in hematopoietic progenitor cells. Current methods for whole-genome mapping of protein-DNA interactions, performed by coupling chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq), require large amounts of starting materials, which precludes their application to rare cell types. Here we combine a high-sensitivity ChIP assay with a new library preparation procedure to map histone modifications in as few as 10,000 cells. We used the technique to characterize mouse hematopoietic progenitors and thereby gain insight into their developmental program.