A compendium of genome-wide hematopoietic transcription factor maps supports the identification of gene regulatory control mechanisms

ObjectiveKey regulators of blood stem cell differentiation into the various mature hematopoietic lineages are commonly encoded by transcription factor genes. Elucidation of transcriptional regulatory mechanisms therefore holds great promise in advancing our understanding of both normal and malignant hematopoiesis. Recent technological advances have enabled the generation of genome-wide transcription factor binding maps using chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq). However, transcription factors operate in a combinatorial fashion suggesting that integrated analysis of genome-wide maps for multiple transcription factors will be essential to fully exploit these new genome-scale data sets.Materials and MethodsHere we have generated a compendium that integrates 53 ChIP-Seq studies covering 30 factors across all major hematopoietic lineages with a total of 754,380 binding peaks. We also used transgenic mouse assays to validate a newly predicted transcriptional enhancer.ResultsIntegrated analysis of all 53 ChIP-Seq studies demonstrated that cell-type identity exerts a larger influence on global transcription factor binding patterns than the nature of the individual transcription factors. Furthermore, regions highlighted by multifactor binding within specific gene loci overlap with known regulatory elements and also provide a useful guide for identifying novel elements, as demonstrated by transgenic analysis of a previously unrecognized enhancer in the Maml3 gene locus.ConclusionsThe ChIP-Seq compendium described here provides a valuable resource for the wider research community by accelerating the discovery of transcriptional mechanisms operating in the hematopoietic system.