Journal
BLOOD
Volume 127, Issue 13, Pages E12-E23Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2015-10-677393
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Funding
- Bloodwise
- Medical Research Council (MRC)
- Leukemia & Lymphoma Society
- Cancer Research UK
- Biotechnology and Biological Sciences Research Council
- National Institute for Health Research Cambridge Biomedical Research Centre
- Wellcome Trust
- Wellcome Trust-MRC Cambridge Stem Cell Institute
- Biotechnology and Biological Sciences Research Council [1352072, BB/I00050X/1, BBS/E/B/000C0405, BBS/E/B/000C0404] Funding Source: researchfish
- British Heart Foundation [RG/09/012/28096] Funding Source: researchfish
- Cancer Research UK [12765] Funding Source: researchfish
- Medical Research Council [MC_PC_12009, MR/M008975/1] Funding Source: researchfish
- National Institute for Health Research [RP-PG-0310-1002, NF-SI-0510-10214, NF-SI-0513-10151] Funding Source: researchfish
- BBSRC [BB/I00050X/1, BBS/E/B/000C0404, BBS/E/B/000C0405] Funding Source: UKRI
- MRC [MR/M008975/1] Funding Source: UKRI
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Comprehensive study of transcriptional control processes will be required to enhance our understanding of both normal and malignant hematopoiesis. Modern sequencing technologies have revolutionized our ability to generate genome-scale expression and histone modification profiles, transcription factor (TF)-binding maps, and also comprehensive chromatin-looping information. Many of these technologies, however, require large numbers of cells, and therefore cannot be applied to rare hematopoietic stem/progenitor cell (HSPC) populations. The stem cell factor-dependent multipotent progenitor cell line HPC-7 represents a well-recognized cell line model for HSPCs. Here we report genome-wide maps for 17 TFs, 3 histone modifications, DNase I hypersensitive sites, and high-resolution promoter-enhancer interactomes in HPC-7 cells. Integrated analysis of these complementary data sets revealed TF occupancy patterns of genomic regions involved in promoter-anchored loops. Moreover, preferential associations between pairs of TFs bound at either ends of chromatin loops led to the identification of 4 previously unrecognized protein-protein interactions between key blood stem cell regulators. All HPC-7 data sets are freely available both through standard repositories and a user-friendly Web interface. Together with previously generated genome-wide data sets, this study integrates HPC-7 data into a genomic resource on par with ENCODE tier 1 cell lines and, importantly, is the only current model with comprehensive genome-scale data that is relevant to HSPC biology.
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