Journal
CELL STEM CELL
Volume 13, Issue 6, Pages 754-768Publisher
CELL PRESS
DOI: 10.1016/j.stem.2013.09.003
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Funding
- FCT [SFRH/BD/33208/2007]
- Swedish Research Council
- Swedish Foundation for Strategic Research
- National Medical Research Council [NMRC/STaR/0001/2008]
- NIH [HL112719]
- Medical Research Council UK
- EuroSyStem
- European Cancer Stem Cell Training, Leukaemia and Lymphoma Research
- UCL Comprehensive Biomedical Research Centre
- Fundação para a Ciência e a Tecnologia [SFRH/BD/33208/2007] Funding Source: FCT
- MRC [MC_U137973817] Funding Source: UKRI
- Cancer Research UK [12796] Funding Source: researchfish
- Medical Research Council [MC_U137973817] Funding Source: researchfish
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We used the paradigmatic GATA-PU.1 axis to explore, at the systems level, dynamic relationships between transcription factor (TF) binding and global gene expression programs as multipotent cells differentiate. We combined global ChIP-seq of GATA1, GATA2, and PU.1 with expression profiling during differentiation to erythroid and neutrophil lineages. Our analysis reveals (1) differential complexity of sequence motifs bound by GATA1, GATA2, and PU.1; (2) the scope and interplay of GATA1 and GATA2 programs within, and during transitions between, different cell compartments, and the extent of their hard-wiring by DNA motifs; (3) the potential to predict gene expression trajectories based on global associations between TF-binding data and target gene expression; and (4) how dynamic modeling of DNA-binding and gene expression data can be used to infer regulatory logic of TF circuitry. This rubric exemplifies the utility of this cross-platform resource for deconvoluting the complexity of transcriptional programs controlling stem/progenitor cell fate in hematopoiesis.
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