| Literature References | 1. HILDEBRAND, D., TIEFENBACH, J., HEINZEL, T., GREZ, M. AND MAURER, A.B.
Multiple regions of ETO cooperate in transcriptional repression.
J.BIOL.CHEM. 276 9889-9895 (2001).
2. DAVIS, J.N., MCGHEE, L. AND MYERS, S.
The ETO (MTG8) gene family.
GENE 303 1-10 (2003).
3. MIYOSHI, H., KOZO, T., SHIMIZU, K., KEIICHIRO, E., MASEKI, N.,
KANEKO, Y., KAMADA, N. AND OHKI, M.
The t(8;21) translocation in acute myeloid leukemia results in production
of an AML1 - MTG8 fusion transcript
EMBO J. 12 2715-2721 (1993).
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| Documentation | Transcriptional activation and repression is required for control of
cell proliferation and differentiation during embryonic development and
homeostasis in the adult organism. Perturbations of these processes can
lead to the development of cancer [1]. The Eight-Twenty-One (ETO) gene
product is able to form complexes with corepressors and deacetylases,
such as nuclear receptor corepressor (N-CoR), which repress transcription
when recruited by transcription factors [2].
The ETO gene derives its name from its association with many cases of
acute myelogenous leukaemia (AML), in which a reciprocal translocation,
t(8;21), brings together a large portion of the ETO gene from chromosome
eight and part of the AML1 gene from chromosome 21. The human ETO gene
family currently comprises three major subfamilies: ETO/myeloid
transforming gene on chromosome 8 (MTG8); myeloid transforming gene related
protein-1 (MTGR1) and myeloid transforming gene on chromosome 16 (MTG16).
ETO proteins are composed of four evolutionarily conserved domains termed
nervy homology regions (NHR) 1-4. NHR1 is thought to stabilise the formation
of high molecular weight complexes, but is not directly responsible for
repressor activity. NHR2 and its flanking sequence comprise the core
repressor domain, which mediates 50% of the wild type repressor activity.
Furthermore, there is evidence that the amphipathic helical structure of
NHR2 promotes the formation of ETO/AML1 homodimers [1]. NHR3 and NHR4 have
been shown to act in concert to bind N-CoR. NHR4 contains two zinc finger
motifs, which are thought to play a role in protein interactions rather
than DNA binding [2].
MTG8 was the first family member to be characterised after being observed as
the chromosome 8 component of the t(8;21) fusion transcript. Northern blot
analysis revealed high levels of MTG8 expression in the brain, with lower
levels present in the lung, heart, testis and ovary. Interestingly, no
detectable levels of MTG8 were observed in haematopoetic tissues, such as
the spleen and thymus [3].
MTG8PROTEIN is a 6-element fingerprint that provides a signature for the
myeloid transforming gene on chromosome 8 (MTG8) protein. The fingerprint
was derived from an initial alignment of 4 sequences: the motifs were drawn
from conserved regions spanning the full alignment length, focusing on
those sections that characterise MTG8 proteins but distinguish them from
closely related ETO family members - motif 1 lies between NHR1 and NHR2;
motif 2 is located within NHR4; motif 3 resides between NHR4 and the
zinc-finger domain; and motifs 4-6 span the C-terminal region. A single
iteration on SPTR40_22f was required to reach convergence, no further
sequences being identified beyond the starting set.
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