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Genome-wide transcriptional control of blood cell type identity

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Transcription factors (TFs) have long been recognised as important regulators of blood cell type identity. Despite advances in the generation of TF binding maps by ChIP-seq, not much is known about the genome-wide impact of TF binding in driving transcriptional programs of multiple cell types. In particular, the rules that govern functional TF binding remain unclear and much remains to be learned about the mechanisms of combinatorial TF interactions, including to what extent constrained spacing and orientation of interacting TFs are critical for regulatory element activity and cell type-specific gene regulation. A more comprehensive understanding of the molecular mechanisms of transcription, however, is recognized to have broad implications for cellular reprogramming and medicine. Using genomics technology, genome sequence analysis and statistical modelling, this study provided greater insight into the role of transcription factors in establishing and maintaining distinct cell-type identity during the process of blood cell maturation. In-depth analysis demonstrated that shared TFs actively participate in the transcriptional programmes of distinct cell types and TFs preferentially bind with constrained spacing.

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