@article{9d76e7ebf6624c26a86a560c0ff4a651,
title = "The SCL 3′ enhancer responds to Hedgehog signaling during hemangioblast specification",
abstract = "Objective: The Hedgehog family of intercellular proteins has a crucial role in embryonic development. Recent experimental data suggests that the Hedgehog pathway may play a role in early hematopoiesis and angiogenesis. Stem cell leukemia (SCL), a basic helix-loop-helix (bHLH) transcription factor, is essential for the specification and function of the hemangioblast. SCL expression in early hematopoietic precursors and endothelium is directed by a 3′ enhancer. We hypothesized that the SCL 3′ enhancer is regulated by Hedgehog signaling during specification of mesoderm towards hemangioblastic fate. Materials and Methods: Whole embryos derived from transgenic mouse lines carrying reporter genes under the regulation of SCL 3′ enhancer were cultured in the presence of active Hedgehog peptide. Hedgehog transcriptional regulation of SCL 3′ enhancer was studied by in vitro and in vivo binding and reporter assays. Results: Hedgehog induced expansion of cells in which the SCL 3′ enhancer was transcriptionally activated. A Gli-binding site within the 3′ enhancer of SCL was identified and Gli1 was demonstrated to bind and transactivate this enhancer in a sequence-dependent manner. We further demonstrated that the core region of the SCL 3′ enhancer is transcriptionally regulated by Hedgehog in-vivo and that the Gli-binding site located in this enhancer is essential for Hedgehog transcriptional regulation in vitro. Conclusion: These findings suggest that SCL may be a direct target of Hedgehog signaling during hemangioblast specification.",
author = "Eldar Hochman and Sarah Kinston and Alon Harmelin and Berthold G{\"o}ttgens and Shai Izraeli",
note = "Funding Information: To Drs. D.R. Gardber, R. Toftgard, P.A. Beachy, R. Auerbach, H. Sasaki, and R. Haffner for providing reagents . To Lev Silberstein, Sandie Piltz, Kathy Knezevic, and Judith Chermesh for technical support. To members of Drs. Izraeli's and Rechavi's laboratory for assistance and discussions. This study was partially funded by the Israel Science Foundation, the Israel Cancer Research Foundation, the Recannati foundation, the Leukaemia Research Fund, BBSRC, and the Cambridge MIT Institute. This work was performed in partial fulfillment of the requirements for the M.D.-Ph.D. thesis of Eldar Hochman, Sackler Faculty of Medicine, Tel Aviv University, Israel. ",
year = "2006",
month = dec,
doi = "10.1016/j.exphem.2006.07.019",
language = "אנגלית",
volume = "34",
pages = "1643.e1--1643.e9",
journal = "Experimental Hematology",
issn = "0301-472X",
publisher = "Elsevier Inc.",
number = "12",
}