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Blood, 1 December 2003, Vol. 102, No. 12, pp. 3954-3962. Prepublished online as a Blood First Edition Paper on August 7, 2003; DOI 10.1182/blood-2003-04-1296. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-04-1296v1 102/12/3954    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cairns, L. A. Articles by Ottolenghi, S. Search for Related Content PubMed PubMed Citation Articles by Cairns, L. A. Articles by Ottolenghi, S. Related Collections Hematopoiesis and Stem Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Kit regulatory elements required for expression in developing hematopoietic and germ cell lineages Linda A. Cairns, Emanuela Moroni, Elena Levantini, Alessandra Giorgetti, Francesca G. Klinger, Simona Ronzoni, Laura Tatangelo, Cecilia Tiveron, Massimo De Felici, Susanna Dolci, Maria Cristina Magli, Barbara Giglioni, and Sergio Ottolenghi From the Dipartimento Biotecnologie e Bioscienze, Università Milano-Bicocca, Milan, Italy; Institute of Biomedical Technologies, National Research Council (CNR), Pisa, Italy; Dipartimento Sanità Pubblica e Biologia Cellulare, Sezione Istologia ed Embriologia, e Anatomia Umana, Università Roma Tor Vergata, Rome, Italy; Istituto Oncologico Europeo, Milan, Italy; Transgenic Mice Service Center, Istituto Regina Elena, Rome, Italy; and Istituto Bioimmagini Fisiologia Molecolare-CNR, Segrate, Italy. The Kit (White) gene encodes the transmembrane receptor of stem cell factor/Kit ligand (KL) and is essential for the normal development/maintenance of pluripotent primordial germ cells (PGCs), hematopoietic stem cells (HSCs), melanoblasts, and some of their descendants. The molecular basis for the transcriptional regulation of Kit during development of these important cell types is unknown. We investigated Kit regulation in hematopoietic cells and PGCs. We identified 6 DNase I hypersensitive sites (HS1-HS6) within the promoter and first intron of the mouse Kit gene and developed mouse lines expressing transgenic green fluorescent protein (GFP) under the control of these regulatory elements. A construct driven by the Kit promoter and including all 6 HS sites is highly expressed during mouse development in Kit+ cells including PGCs and hematopoietic progenitors (erythroid blast-forming units and mixed colony-forming units). In contrast, the Kit promoter alone (comprising HS1) is sufficient to drive low-level GFP expression in PGCs, but unable to function in hematopoietic cells. Hematopoietic expression further requires the addition of the intronproximal HS2 fragment; HS2 also greatly potentiates the activity in PGCs. Thus, HS2 acts as an enhancer integrating transcriptional signals common to 2 developmentally unrelated stem cell/progenitor lineages. Optimal hematopoietic expression further requires HS3-HS6. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Mithraprabhu and K. L Loveland Control of KIT signalling in male germ cells: what can we learn from other systems? Reproduction, November 1, 2009; 138(5): 743 - 757. [Abstract] [Full Text] [PDF] J. Ferreira-Martins, C. Rondon-Clavo, D. Tugal, J. A. Korn, R. Rizzi, M. E. Padin-Iruegas, S. Ottolenghi, A. De Angelis, K. Urbanek, N. Ide-Iwata, et al. Spontaneous Calcium Oscillations Regulate Human Cardiac Progenitor Cell Growth Circ. Res., October 9, 2009; 105(8): 764 - 774. [Abstract] [Full Text] [PDF] F. Cerisoli, L. Cassinelli, G. Lamorte, S. Citterio, F. Bertolotti, M. C. Magli, and S. Ottolenghi Green fluorescent protein transgene driven by Kit regulatory sequences is expressed in hematopoietic stem cells Haematologica, March 1, 2009; 94(3): 318 - 325. [Abstract] [Full Text] [PDF] D. Filipponi, R. M. Hobbs, S. Ottolenghi, P. Rossi, E. A. Jannini, P. P. Pandolfi, and S. Dolci Repression of kit Expression by Plzf in Germ Cells Mol. Cell. Biol., October 1, 2007; 27(19): 6770 - 6781. [Abstract] [Full Text] [PDF] A. K. Todd, S. M. Haider, G. N. Parkinson, and S. Neidle Sequence occurrence and structural uniqueness of a G-quadruplex in the human c-kit promoter Nucleic Acids Res., September 27, 2007; 35(17): 5799 - 5808. [Abstract] [Full Text] [PDF] F. Cerisoli, L. Cassinelli, G. Lamorte, S. Citterio, M. C. Magli, and S. Ottolenghi Efficient Expression of a Kit/GFP Transgene in Hematopoietic Stem Cells of Mouse Fetal Liver and Bone Marrow. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 4159 - 4159. [Abstract] [PDF] G. Berrozpe, V. Agosti, C. Tucker, C. Blanpain, K. Manova, and P. Besmer A Distant Upstream Locus Control Region Is Critical for Expression of the Kit Receptor Gene in Mast Cells Mol. Cell. Biol., August 1, 2006; 26(15): 5850 - 5860. [Abstract] [Full Text] [PDF] J.-Y. Rho, K. Yu, J.-S. Han, J.-I. Chae, D.-B. Koo, H.-S. Yoon, S.-Y. Moon, K.-K. Lee, and Y.-M. Han Transcriptional profiling of the developmentally important signalling pathways in human embryonic stem cells Hum. Reprod., February 1, 2006; 21(2): 405 - 412. [Abstract] [Full Text] [PDF] A. Frattini, H. C. Blair, M. G. Sacco, F. Cerisoli, F. Faggioli, E. M. Cato, A. Pangrazio, A. Musio, F. Rucci, C. Sobacchi, et al. Rescue of ATPa3-deficient murine malignant osteopetrosis by hematopoietic stem cell transplantation in utero PNAS, October 11, 2005; 102(41): 14629 - 14634. [Abstract] [Full Text] [PDF] M. Wouters, K. Smans, and J.-M. 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