Lara-Astiaso, D. et al. Science 345, 943–949 (2014).

Specific histone modifications are associated with the position and activity of regulatory regions in the genome and can be localized using chromatin immunoprecipitation (ChIP). However, ChIP requires a large number of cells, whereas many dynamic biological events involve small, transient cell populations. Lara-Astiaso et al. developed an indexing-first ChIP (iChIP) procedure in which total chromatin from individual fixed and cell-sorted samples is ligated to DNA barcodes. iChIP avoids low-input enzymatic steps and is compatible with large-scale pooling, making it sensitive and reproducible even from just a few hundred cells. The authors used iChIP to characterize the dynamics of thousands of enhancer and promoter regions by following four chromatin modifications along 16 well-defined steps of hematopoietic differentiation. They identified tens of thousands of de novo lineage-specific enhancers and used gene expression profiling to relate chromatin dynamics to a transcription factor network.