Regulation of flt3 gene expression in haematopoietic and leukaemic stem cells
作者： Giacomo Volpe
DOI:
关键词: Histone 、 Haematopoiesis 、 Methylation 、 Genetics 、 Epigenetics 、 Receptor tyrosine kinase 、 Cell culture 、 Gene 、 Cell biology 、 Stem cell 、 Biology
摘要: The interaction between the tyrosine kinase receptor Flt3 and its ligand leads to signalling during commitment of haematopoietic stem cells (HSCs). Constitutive activation Flt3/FL pathway is a key factor in enhanced survival expansion acute myeloid leukaemia (AML). Although there extensive knowledge regarding mutations leading constitutive activity, molecular mechanisms underlying regulation \(flt3\) gene HSCs, how such might be altered leukaemia, are still poorly understood. Here, by using HSC leukaemic cell lines, I locate several regulatory elements locus DNaseI mapping have characterized their epigenetic environment. Analysis methylation acetylation status histones H3 H4 around \(flt3 cis\)-regulatory regions highlights distinct combination modifications specific AML region that distinguishes Flt3\(^-\) Flt3\(^+\) stages differentiation. Moreover, show link \(in vivo\) binding C/EBP c-Myb on remodelling differential cells. Finally, identify histone modifiers TIP60 CBP as potential mediators
bl.uk参考文章(186)
Hilary J. McKenna, Kim L. Stocking, Robert E. Miller, Kenneth Brasel, Thibaut De Smedt, Eugene Maraskovsky, Charles R. Maliszewski, David H. Lynch, Jeffrey Smith, Bali Pulendran, Eileen R. Roux, Mark Teepe, Stewart D. Lyman, Jacques J. Peschon, Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Blood. ,vol. 95, pp. 3489- 3497 ,(2000) , 10.1182/BLOOD.V95.11.3489
L. Sun, A. Liu, K. Georgopoulos, Zinc finger-mediated protein interactions modulate Ikaros activity, a molecular control of lymphocyte development. The EMBO Journal. ,vol. 15, pp. 5358- 5369 ,(1996) , 10.1002/J.1460-2075.1996.TB00920.X
Jos Domen, The role of apoptosis in regulating hematopoietic stem cell numbers. Apoptosis. ,vol. 6, pp. 239- 252 ,(2001) , 10.1023/A:1011347623402
Lyman, Biology of flt3 ligand and receptor. International Journal of Hematology. ,vol. 62, pp. 63- 73 ,(1995) , 10.1016/0925-5710(95)00389-A
P Erickson, J Gao, KS Chang, T Look, E Whisenant, S Raimondi, R Lasher, J Trujillo, J Rowley, H Drabkin, Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt. Blood. ,vol. 80, pp. 1825- 1831 ,(1992) , 10.1182/BLOOD.V80.7.1825.BLOODJOURNAL8071825
S. R. McKercher, B. E. Torbett, K. L. Anderson, G. W. Henkel, D. J. Vestal, H. Baribault, M. Klemsz, A. J. Feeney, G. E. Wu, C. J. Paige, R. A. Maki, Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities. The EMBO Journal. ,vol. 15, pp. 5647- 5658 ,(1996) , 10.1002/J.1460-2075.1996.TB00949.X
Toshiyuki Kawashima, Ken Murata, Shizuo Akira, Yukio Tonozuka, Yukinori Minoshima, Sizhou Feng, Hidetoshi Kumagai, Hiromichi Tsuruga, Yasuo Ikeda, Shigetaka Asano, Tetsuya Nosaka, Toshio Kitamura, STAT5 Induces Macrophage Differentiation of M1 Leukemia Cells Through Activation of IL-6 Production Mediated by NF-κB p65 The Journal of Immunology. ,vol. 167, pp. 3652- 3660 ,(2001) , 10.4049/JIMMUNOL.167.7.3652
Allan Spradling, Daniela Drummond-Barbosa, Toshie Kai, Stem cells find their niche Nature. ,vol. 414, pp. 98- 104 ,(2001) , 10.1038/35102160
CE Carow, M Levenstein, SH Kaufmann, J Chen, S Amin, P Rockwell, L Witte, MJ Borowitz, CI Civin, D Small, Expression of the hematopoietic growth factor receptor FLT3 (STK-1/Flk2) in human leukemias. Blood. ,vol. 87, pp. 1089- 1096 ,(1996) , 10.1182/BLOOD.V87.3.1089.BLOODJOURNAL8731089
Johan van der Vlag, Arie P. Otte, Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation. Nature Genetics. ,vol. 23, pp. 474- 478 ,(1999) , 10.1038/70602