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.