|
|
Prepublished online as a Blood First Edition Paper on May 31, 2002; DOI 10.1182/blood-2002-02-0568.
 Previous Article | Table of Contents | Next Article 
Blood, 1 October 2002, Vol. 100, No. 7, pp. 2430-2440
HEMATOPOIESIS
The SCL complex regulates c-kit expression in
hematopoietic cells through functional interaction with Sp1
Eric Lécuyer,
Sabine Herblot,
Marianne Saint-Denis,
Richard Martin,
C. Glenn Begley,
Catherine Porcher,
Stuart H. Orkin, and
Trang Hoang
From the Clinical Research Institute of Montreal and
from the Departments of Pharmacology, Biochemistry, and Molecular
Biology, Université de Montréal, Quebec, Canada; the
Telethon Institute for Child Health Research, Center for Child Research
and Western Australian Institute for Medical Research, The
University of Western Australia, West Perth, Australia; the Molecular
Haematology Unit, Weatherall Institute of Molecular Medicine, John
Radcliffe Hospital, Headington, Oxford, United Kingdom; and the Howard
Hughes Medical Institute, The Children's Hospital, Harvard Medical
School, Boston, MA.
The combinatorial interaction among transcription factors
is believed to determine hematopoietic cell fate. Stem cell
leukemia (SCL, also known as TAL1 [T-cell acute
lymphoblastic leukemia 1]) is a tissue-specific basic helix-loop-helix
(bHLH) factor that plays a central function in
hematopoietic development; however, its target genes and molecular mode
of action remain to be elucidated. Here we show that SCL and the c-Kit
receptor are coexpressed in hematopoietic progenitors at the
single-cell level and that SCL induces c-kit in chromatin,
as ectopic SCL expression in transgenic mice sustains c-kit
transcription in developing B lymphocytes, in which both genes are
normally down-regulated. Through transient transfection assays and
coimmunoprecipitation of endogenous proteins, we define the role of SCL
as a nucleation factor for a multifactorial complex (SCL complex) that
specifically enhances c-kit promoter activity without
affecting the activity of myelomonocytic promoters. This complex,
containing hematopoietic-specific (SCL, Lim-only 2 (LMO2),
GATA-1/GATA-2) and ubiquitous (E2A,
LIM- domain binding protein 1 [Ldb-1]) factors, is
tethered to DNA via a specificity protein 1 (Sp1) motif,
through direct interactions between elements of the SCL complex and the
Sp1 zinc finger protein. Furthermore, we demonstrate by chromatin
immunoprecipitation that SCL, E2A, and Sp1 specifically co-occupy the
c-kit promoter in vivo. We therefore conclude that
c-kit is a direct target of the SCL complex. Proper
activation of the c-kit promoter depends on the
combinatorial interaction of all members of the complex. Since SCL is
down-regulated in maturing cells while its partners remain expressed,
our observations suggest that loss of SCL inactivates the SCL complex,
which may be an important event in the differentiation of pluripotent
hematopoietic cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
N. K. Wilson, D. Miranda-Saavedra, S. Kinston, N. Bonadies, S. D. Foster, F. Calero-Nieto, M. A. Dawson, I. J. Donaldson, S. Dumon, J. Frampton, et al.
The transcriptional program controlled by the stem cell leukemia gene Scl/Tal1 during early embryonic hematopoietic development
Blood,
May 28, 2009;
113(22):
5456 - 5465.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Felli, F. Pedini, P. Romania, M. Biffoni, O. Morsilli, G. Castelli, S. Santoro, S. Chicarella, A. Sorrentino, C. Peschle, et al.
MicroRNA 223-dependent expression of LMO2 regulates normal erythropoiesis
Haematologica,
April 1, 2009;
94(4):
479 - 486.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Tripic, W. Deng, Y. Cheng, Y. Zhang, C. R. Vakoc, G. D. Gregory, R. C. Hardison, and G. A. Blobel
SCL and associated proteins distinguish active from repressive GATA transcription factor complexes
Blood,
March 5, 2009;
113(10):
2191 - 2201.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. T. Kassouf, H. Chagraoui, P. Vyas, and C. Porcher
Differential use of SCL/TAL-1 DNA-binding domain in developmental hematopoiesis
Blood,
August 15, 2008;
112(4):
1056 - 1067.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-R. Landry, S. Kinston, K. Knezevic, M. F.T.R. de Bruijn, N. Wilson, W. T. Nottingham, M. Peitz, F. Edenhofer, J. E. Pimanda, K. Ottersbach, et al.
Runx genes are direct targets of Scl/Tal1 in the yolk sac and fetal liver
Blood,
March 15, 2008;
111(6):
3005 - 3014.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Lecuyer, S. Lariviere, M.-C. Sincennes, A. Haman, R. Lahlil, M. Todorova, M. Tremblay, B. C. Wilkes, and T. Hoang
Protein Stability and Transcription Factor Complex Assembly Determined by the SCL-LMO2 Interaction
J. Biol. Chem.,
November 16, 2007;
282(46):
33649 - 33658.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Grondin, M. Lefrancois, M. Tremblay, M. Saint-Denis, A. Haman, K. Waga, A. Bedard, D. G. Tenen, and T. Hoang
c-Jun Homodimers Can Function as a Context-Specific Coactivator
Mol. Cell. Biol.,
April 15, 2007;
27(8):
2919 - 2933.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. J. Patterson, M. Gering, C. E. Eckfeldt, A. R. Green, C. M. Verfaillie, S. C. Ekker, and R. Patient
The transcription factors Scl and Lmo2 act together during development of the hemangioblast in zebrafish
Blood,
March 15, 2007;
109(6):
2389 - 2398.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. B. de la Grange, F. Armstrong, V. Duval, M.-C. Rouyez, N. Goardon, P.-H. Romeo, and F. Pflumio
Low SCL/TAL1 expression reveals its major role in adult hematopoietic myeloid progenitors and stem cells
Blood,
November 1, 2006;
108(9):
2998 - 3004.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Li, J.-W. Xiong, C. S. Shelley, H. Park, and M. A. Arnaout
The transcription factor ZBP-89 controls generation of the hematopoietic lineage in zebrafish and mouse embryonic stem cells
Development,
September 15, 2006;
133(18):
3641 - 3650.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Palomero, D. T. Odom, J. O'Neil, A. A. Ferrando, A. Margolin, D. S. Neuberg, S. S. Winter, R. S. Larson, W. Li, X. S. Liu, et al.
Transcriptional regulatory networks downstream of TAL1/SCL in T-cell acute lymphoblastic leukemia
Blood,
August 1, 2006;
108(3):
986 - 992.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Talora, S. Cialfi, C. Oliviero, R. Palermo, M. Pascucci, L. Frati, A. Vacca, A. Gulino, and I. Screpanti
Cross talk among Notch3, pre-TCR, and Tal1 in T-cell development and leukemogenesis
Blood,
April 15, 2006;
107(8):
3313 - 3320.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. H. Schuh, A. J. Tipping, A. J. Clark, I. Hamlett, B. Guyot, F. J. Iborra, P. Rodriguez, J. Strouboulis, T. Enver, P. Vyas, et al.
ETO-2 Associates with SCL in Erythroid Cells and Megakaryocytes and Provides Repressor Functions in Erythropoiesis
Mol. Cell. Biol.,
December 1, 2005;
25(23):
10235 - 10250.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-R. Landry, S. Kinston, K. Knezevic, I. J. Donaldson, A. R. Green, and B. Gottgens
Fli1, Elf1, and Ets1 regulate the proximal promoter of the LMO2 gene in endothelial cells
Blood,
October 15, 2005;
106(8):
2680 - 2687.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Reynaud, E. Ravet, M. Titeux, F. Mazurier, L. Renia, A. Dubart-Kupperschmitt, P.-H. Romeo, and F. Pflumio
SCL/TAL1 expression level regulates human hematopoietic stem cell self-renewal and engraftment
Blood,
October 1, 2005;
106(7):
2318 - 2328.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Maki, T. Yamagata, T. Asai, I. Yamazaki, H. Oda, H. Hirai, and K. Mitani
Dysplastic definitive hematopoiesis in AML1/EVI1 knock-in embryos
Blood,
September 15, 2005;
106(6):
2147 - 2155.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Hall, N. J. Slater, C. G. Begley, J. M. Salmon, L. J. Van Stekelenburg, M. P. McCormack, S. M. Jane, and D. J. Curtis
Functional but Abnormal Adult Erythropoiesis in the Absence of the Stem Cell Leukemia Gene
Mol. Cell. Biol.,
August 1, 2005;
25(15):
6355 - 6362.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Munugalavadla, L. C. Dore, B. L. Tan, L. Hong, M. Vishnu, M. J. Weiss, and R. Kapur
Repression of c-Kit and Its Downstream Substrates by GATA-1 Inhibits Cell Proliferation during Erythroid Maturation
Mol. Cell. Biol.,
August 1, 2005;
25(15):
6747 - 6759.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Nishiyama, T. Ito, M. Nishiyama, S. Masaki, K. Maeda, N. Nakano, W. Ng, K. Fukuyama, M. Yamamoto, K. Okumura, et al.
GATA-1 is required for expression of Fc{varepsilon}RI on mast cells: analysis of mast cells derived from GATA-1 knockdown mouse bone marrow
Int. Immunol.,
July 1, 2005;
17(7):
847 - 856.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Zhang, K. J. Payne, Y. Zhu, M. A. Price, Y. K. Parrish, E. Zielinska, L. W. Barsky, and G. M. Crooks
SCL Expression at Critical Points in Human Hematopoietic Lineage Commitment
Stem Cells,
June 1, 2005;
23(6):
852 - 860.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Wen, S. Huang, S. D. Pack, X. Yu, S. J. Brandt, and C. T. Noguchi
Tal1/SCL Binding to Pericentromeric DNA Represses Transcription
J. Biol. Chem.,
April 1, 2005;
280(13):
12956 - 12966.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Valverde-Garduno, B. Guyot, E. Anguita, I. Hamlett, C. Porcher, and P. Vyas
Differences in the chromatin structure and cis-element organization of the human and mouse GATA1 loci: implications for cis-element identification
Blood,
November 15, 2004;
104(10):
3106 - 3116.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. M. Schlaeger, A. Schuh, S. Flitter, A. Fisher, H. Mikkola, S. H. Orkin, P. Vyas, and C. Porcher
Decoding Hematopoietic Specificity in the Helix-Loop-Helix Domain of the Transcription Factor SCL/Tal-1
Mol. Cell. Biol.,
September 1, 2004;
24(17):
7491 - 7502.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Beland, N. Pilon, M. Houle, K. Oh, J.-R. Sylvestre, P. Prinos, and D. Lohnes
Cdx1 Autoregulation Is Governed by a Novel Cdx1-LEF1 Transcription Complex
Mol. Cell. Biol.,
June 1, 2004;
24(11):
5028 - 5038.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Ravet, D. Reynaud, M. Titeux, B. Izac, S. Fichelson, P.-H. Romeo, A. Dubart-Kupperschmitt, and F. Pflumio
Characterization of DNA-binding-dependent and -independent functions of SCL/TAL1 during human erythropoiesis
Blood,
May 1, 2004;
103(9):
3326 - 3335.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Curtis, M. A. Hall, L. J. Van Stekelenburg, L. Robb, S. M. Jane, and C. G. Begley
SCL is required for normal function of short-term repopulating hematopoietic stem cells
Blood,
May 1, 2004;
103(9):
3342 - 3348.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Lahlil, E. Lecuyer, S. Herblot, and T. Hoang
SCL Assembles a Multifactorial Complex That Determines Glycophorin A Expression
Mol. Cell. Biol.,
February 15, 2004;
24(4):
1439 - 1452.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Gering, Y. Yamada, T. H. Rabbitts, and R. K. Patient
Lmo2 and Scl/Tal1 convert non-axial mesoderm into haemangioblasts which differentiate into endothelial cells in the absence of Gata1
Development,
December 22, 2003;
130(25):
6187 - 6199.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. A. Cairns, E. Moroni, E. Levantini, A. Giorgetti, F. G. Klinger, S. Ronzoni, L. Tatangelo, C. Tiveron, M. De Felici, S. Dolci, et al.
Kit regulatory elements required for expression in developing hematopoietic and germ cell lineages
Blood,
December 1, 2003;
102(12):
3954 - 3962.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Xu, S. Huang, L.-S. Chang, A. D. Agulnick, and S. J. Brandt
Identification of a TAL1 Target Gene Reveals a Positive Role for the LIM Domain-Binding Protein Ldb1 in Erythroid Gene Expression and Differentiation
Mol. Cell. Biol.,
November 1, 2003;
23(21):
7585 - 7599.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. F. Calkhoven, C. Muller, R. Martin, G. Krosl, T. Hoang, and A. Leutz
Translational control of SCL-isoform expression in hematopoietic lineage choice
Genes & Dev.,
April 15, 2003;
17(8):
959 - 964.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Tremblay, S. Herblot, E. Lecuyer, and T. Hoang
Regulation of pTalpha Gene Expression by a Dosage of E2A, HEB, and SCL
J. Biol. Chem.,
April 4, 2003;
278(15):
12680 - 12687.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Gabbianelli, U. Testa, A. Massa, O. Morsilli, E. Saulle, N. M. Sposi, E. Petrucci, G. Mariani, and C. Peschle
HbF reactivation in sibling BFU-E colonies: synergistic interaction of kit ligand with low-dose dexamethasone
Blood,
April 1, 2003;
101(7):
2826 - 2832.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
