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Molecular and Cellular Biology, February 2004, p. 1439-1452, Vol. 24, No. 4
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.4.1439-1452.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

SCL Assembles a Multifactorial Complex That Determines Glycophorin A Expression

Rachid Lahlil, Eric Lécuyer, Sabine Herblot, and Trang Hoang*

Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, and Departments of Pharmacology, Biochemistry, and Molecular Biology and Institute of Immunovirology and Cancer, University of Montréal, Montréal, Québec H3C 3J7, Canada

Received 7 July 2003/ Returned for modification 22 August 2003/ Accepted 7 November 2003

SCL/TAL1 is a hematopoietic-specific transcription factor of the basic helix-loop-helix (bHLH) family that is essential for erythropoiesis. Here we identify the erythroid cell-specific glycophorin A gene (GPA) as a target of SCL in primary hematopoietic cells and show that SCL occupies the GPA locus in vivo. GPA promoter activation is dependent on the assembly of a multifactorial complex containing SCL as well as ubiquitous (E47, Sp1, and Ldb1) and tissue-specific (LMO2 and GATA-1) transcription factors. In addition, our observations suggest functional specialization within this complex, as SCL provides its HLH protein interaction motif, GATA-1 exerts a DNA-tethering function through its binding to a critical GATA element in the GPA promoter, and E47 requires its N-terminal moiety (most likely entailing a transactivation function). Finally, endogenous GPA expression is disrupted in hematopoietic cells through the dominant-inhibitory effect of a truncated form of E47 (E47-bHLH) on E-protein activity or of FOG (Friend of GATA) on GATA activity or when LMO2 or Ldb-1 protein levels are decreased. Together, these observations reveal the functional complementarities of transcription factors within the SCL complex and the essential role of SCL as a nucleation factor within a higher-order complex required to activate gene GPA expression.


* Corresponding author. Mailing address: Institut de Recherche en Immunovirologie et Cancérologie, Université de Montréal, P.O. Box 6128, Centre-ville Branch, Montréal, Québec H3C 2J7, Canada. Phone: (514) 343-6870. Fax: (514) 343-6945. E-mail: trang.hoang{at}umontreal.ca.


Molecular and Cellular Biology, February 2004, p. 1439-1452, Vol. 24, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.4.1439-1452.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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