Journal article

The transcriptional program controlled by the stem cell leukemia gene Scl/Tal1 during early embryonic hematopoietic development

Nicola K Wilson, Diego Miranda-Saavedra, Sarah Kinston, Nicolas Bonadies, Samuel D Foster, Fernando Calero-Nieto, Mark A Dawson, Ian J Donaldson, Stephanie Dumon, Jonathan Frampton, Rekin's Janky, Xiao-Hong Sun, Sarah A Teichmann, Andrew J Bannister, Berthold Goettgens

BLOOD | AMER SOC HEMATOLOGY | Published : 2009


The basic helix-loop-helix transcription factor Scl/Tal1 controls the development and subsequent differentiation of hematopoietic stem cells (HSCs). However, because few Scl target genes have been validated to date, the underlying mechanisms have remained largely unknown. In this study, we have used ChIP-Seq technology (coupling chromatin immunoprecipitation with deep sequencing) to generate a genome-wide catalog of Scl-binding events in a stem/progenitor cell line, followed by validation using primary fetal liver cells and comprehensive transgenic mouse assays. Transgenic analysis provided in vivo validation of multiple new direct Scl target genes and allowed us to reconstruct an in vivo va..

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Awarded by Medical Research Council

Funding Acknowledgements

We thank Cheng-Eng Ang and Richard Dixon (Medical Solution), as well as Yongjun Zhao and Martin Hirst (British Columbia Cancer Agency Genome Sciences Center, Vancouver, BC) for expert managing of Illumina sequencing runs; Duncan Odom and Dominic Schmidt for advice on processing samples for ChIP-Seq; and John Pimanda for critically reading the manuscript.This work was supported by the Leukaemia Research Fund, London, United Kingdom: Leukemia & Lymphoma Foundation, New York, NY; Cancer Research UK, London, United Kingdom; Newton Trust, Cambridge, United Kingdom; United Kingdom Medical Research Council, London, United Kingdom; and Cambridge Cancer Center, Cambridge, United Kingdom.