Finding partners to play the music of regulation.

In this issue of Blood, Wilson et al generate and analyze a treasure trove of epigenetic data, such as transcription factor occupancy, histone modifications, and chromatin interaction frequencies, genome-wide (ie, epigenomic data), in a cell line model of hematopoietic stem/progenitor cells (HSPCs). To appreciate the importance of these data, consider an analogy of gene expression being a song or symphony (transcripts) played by musicians (transcription factors and transcriptional machinery) reading the score encoded in the genome sequence. Previous studies revealed the positions of a few transcription factors across the genome, so we only knew about, for example, the violinists and oboists. No wonder we did not understand how the music was being generated (how expression was regulated). By mapping the sites of occupancy of many more transcription factors (now a total of 29), as well as positions of 4 histone modifications and DNase hypersensitive sites, Wilson et al reveal many more of the players and their partners. Furthermore, their data on 3-dimensional interaction frequencies of chromatin show how groups of musicians (protein complexes) come together in an orchestra to read the score and perform a symphony.