1: Int J Biochem Cell Biol. 2001 Apr;33(4):391-407. 

The Ets family contains transcriptional activators and repressors involved in
angiogenesis.

Lelievre E, Lionneton F, Soncin F, Vandenbunder B.

Institut de Biologie de Lille, 1, rue du Professeur Calmette, BP 447, 59021,
Lille Cedex, France.

The Ets family contains a growing number of transcriptional activators and
inhibitors, which activity is regulated by phosphorylation and protein-protein
interactions. Among these factors, Ets1, Erg1 and Fli1 are expressed in
endothelial cells during angiogenesis in normal and pathological development.
The expression of these transcription factors is regulated by angiogenic factors
in cultured endothelial cells, as well as by various stresses occurring during
angiogenesis. Transfection experiments and transgenic mice analysis revealed
that Ets family members are involved in the transcriptional regulation of
endothelial specific genes such as those encoding Tie1 and -2, VEGFR1 and -2 and
VE-Cadherin. In vitro studies plead for a role of Ets family members in
endothelial cell adhesion, spreading and motility. Gene inactivation experiments
show that Ets1 is dispensable for embryonic development. The phenotype of
knocked-out embryos indicates that Tel is required for maintenance of the
developing vascular network in the yolk sac. Altogether, we suggest that Ets
family members act both positively and negatively during the different steps of
the angiogenic process. The regulation of the initiation of gene transcription
arises from the combined activity of different transcriptional regulators.
Therefore very few transcription factors are specific for a physiological
process, or a given cell type. The transcriptional network that regulates blood
vessel formation involves transcription factors which are expressed in a variety
of situations. The Lung Kruppel Like Factor (LKLF) which is required for blood
vessel stabilisation during murine development is also expressed in the
primitive vertebrae and in the lung of the adult (C.T. Kuo, M.L. Veselits, K.P.
Barton, M.M. Lu, C. Clendenin, J.M. Leiden, The LKLF transcription factor is
required for normal tunica media formation and blood vessel stabilisation during
murine embryogenesis, Genes Dev. 11 (22) (1997) 2996-3006). Scl/Tal1 which is
essential for angiogenic remodelling of the yolk sac capillary network (J.E.
Visvader, Y. Fujiwara, S.H. Orkin, Unsuspected role for the T-cell leukemia
protein SCL/tal-1 in vascular development, Genes Dev. 12 (4) (1998) 473-479), is
involved in blood cell development and is also expressed in the developing
brain. The EPAS transcription factor which was thought to be endothelial cell
specific in the mouse embryo (H. Tian, S.L. McKnight, D.W. Russell, Endothelial
PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in
endothelial cells, Genes Dev. 11 (1) (1997) 72-82) is also expressed in the
liver, kidney and cells of the sympathetic nervous system of the chick embryo
(J. Favier, H. Kempf, P. Corvol, J.M. Gasc, Cloning and expression pattern of
EPAS1 in the chicken embryo. Colocalization with tyrosine hydroxylase, FEBS
Lett. 462 (1-2) (1999) 19-24). Ets1, which expression was originally detected in
lymphoid cells of adult tissues, has been the first transcription factor to be
identified in endothelial cells during angiogenesis in the embryo (B.
Vandenbunder, L. Pardanaud, T. Jaffredo, M.A. Mirabel, D. Stehelin,
Complementary patterns of expression of c-etsl, c-myb and c-myc in the
blood-forming system of the chick embryo, Development 107 (1989) 265-274 [5])
and in tumours (N. Wernert, M.B. Raes, P. Lassalle, M.P. Dehouck, B. Gosselin,
B. Vandenbunder, D. Stehelin, The c-ets 1 proto-oncogene is a transcription
factor expressed in endothelial cells during tumor vascularisation and other
forms of angiogenesis in man, Am. J. Path. 140 (1992) 119-127 [6]). Since then,
the Ets family has extended and this review will emphasise the relationships
between these factors and angiogenesis.

Publication Types:
    Review
    Review, Tutorial

PMID: 11312108 [PubMed - indexed for MEDLINE]


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2: Blood. 1995 Jan 15;85(2):379-90. 

Differential regulation of macrophage differentiation in response to leukemia
inhibitory factor/oncostatin-M/interleukin-6: the effect of enforced expression
of the SCL transcription factor.

Tanigawa T, Nicola N, McArthur GA, Strasser A, Begley CG.

Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital,
Victoria, Australia.

The physiologic program of macrophage differentiation normally proceeds in a
coordinated manner in response to several different growth factors. Although the
utilization of common receptor subunits may explain in part overlapping biologic
functions, mechanisms by which unique actions are mediated remain obscure. We
examined growth factor-induced macrophage differentiation in M1 leukemia cells
that simultaneously display receptors for interleukin-6 (IL-6), leukemia
inhibitory factor (LIF) and Oncostatin-M (OSM). Differentiation induced by all
three factors was associated with decreased expression of transcription factors
myb and SCL, increased expression of macrophage markers, and suppression of
proliferation. Cell lines were established in which SCL expression was enforced.
In the absence of growth factors, cells were indistinguishable from parental
cells. However, LIF (or OSM)-induced macrophage differentiation was perturbed;
there was failure to undergo morphologic differentiation, disturbed expression
of lysozyme and Mac1 alpha, and failure to suppress proliferation. Surprisingly
the perturbation of macrophage differentiation did not apply to induced
expression of macrophage colony-stimulating factor (M-CSF) or granulocyte colony
stimulating factor (G-CSF) receptors. This dissociation of elements normally
coordinated in a macrophage differentiation program applied at a clonal level.
There was no disturbance of IL-6-induced macrophage differentiation. These data
directly implicate SCL in components of the macrophage differentiation program
(suggesting that LIF receptor/gp130 heterodimers utilize an SCL-inhibitable
pathway while gp130 homodimers do not) and demonstrate differential-regulation
of components of the mature macrophage phenotype.

PMID: 7811994 [PubMed - indexed for MEDLINE]


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3: Oncogene. 1992 Apr;7(4):653-60. 

Erratum in:
    Oncogene 1992 Jul;7(7):1459.

SCL is coexpressed with GATA-1 in hemopoietic cells but is also expressed in
developing brain.

Green AR, Lints T, Visvader J, Harvey R, Begley CG.

Department of Haematology, Cambridge, UK.

The SCL gene encodes a putative transcription factor with a basic
helix-loop-helix (B-HLH) motif and is known to be predominantly expressed in
erythroid cells. Here we also demonstrate expression of SCL mRNA in normal mast
cells, mast cell lines and megakaryocytic cell lines. SCL is therefore expressed
in the same three lineages as GATA-1, a well-recognized hemopoietic
transcription factor. SCL and GATA-1 mRNA were also co-expressed in interleukin
3-dependent primitive myeloid lines. In murine erythroleukemia (MEL) cells SCL
and GATA-1 underwent coordinated biphasic modulation during hexamethylene
bisacetamide (HMBA)-induced erythroid differentiation. The kinetics of SCL and
GATA-1 mRNA expression was inversely correlated with changes in ID, a negative
regulator of B-HLH proteins, and was distinct from changes in MYC, MYB and
erythropoietin receptor transcripts. During myeloid differentiation of K562
cells, SCL and GATA-1 mRNA levels also underwent biphasic modulation. Thus SCL
and GATA-1 are coordinately expressed in multiple hemopoietic lineages and
coordinately regulated during induced erythroid and myeloid differentiation. In
nonhemopoietic tissues SCL was only detected in adult and developing brain where
GATA-1 is reportedly not expressed. In day 14.5 embryos analysed by in situ
hybridization, SCL transcripts were detected in post-mitotic neurons in the
metencephalon and roof of the mesencephalon. This suggests a previously
unexpected role for SCL in neural differentiation.

PMID: 1565464 [PubMed - indexed for MEDLINE]


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