1: Mol Cell Biol. 2004 Feb;24(4):1439-52. 

SCL assembles a multifactorial complex that determines glycophorin A expression.

Lahlil R, Lecuyer E, Herblot S, Hoang T.

Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada.

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.

PMID: 14749362 [PubMed - indexed for MEDLINE]


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2: Blood. 2002 Oct 1;100(7):2430-40. 

The SCL complex regulates c-kit expression in hematopoietic cells through
functional interaction with Sp1.

Lecuyer E, Herblot S, Saint-Denis M, Martin R, Begley CG, Porcher C, Orkin SH,
Hoang T.

Clinical Research Institute of Montreal and from the Departments of
Pharmacology, Biochemistry, and Molecular Biology, Universite de Montreal,
Quebec, Canada.

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.

PMID: 12239153 [PubMed - indexed for MEDLINE]


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