PMID- 10597226
OWN - NLM
STAT- MEDLINE
DCOM- 20000110
LR  - 20061115
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 46
DP  - 1999 Nov 4
TI  - Characterization of the human and mouse ETV1/ER81 transcription factor genes:
      role of the two alternatively spliced isoforms in the human.
PG  - 6278-86
AB  - The Ets transcription factors of the PEA3 group--E1AF/PEA3, ETV1/ER81 and
      ERM--are almost identical in the ETS DNA-binding and the transcriptional acidic
      domains. To accelerate our understanding of the molecular basis of putative
      diseases linked to ETV1 such as Ewing's sarcoma we characterized the human ETV1
      and the mouse ER81 genes. We showed that these genes are both encoded by 13 exons
      in more than 90 kbp genomic DNA, and that the classical acceptor and donor
      splicing sites are present in each junction except for the 5' donor site of
      intron 9 where GT is replaced by TT. The genomic organization of the ETS and
      acidic domains in the human ETV1 and mouse ER81 (localized to chromosome 12)
      genes is similar to that observed in human ERM and human E1AF/PEA3 genes.
      Moreover, as in human ERM and human E1AF/PEA3 genes, a first untranslated exon is
      upstream from the first methionine, and the mouse ER81 gene transcription is
      regulated by a 1.8 kbp of genomic DNA upstream from this exon. In human, the
      alternative splicing of the ETV1 gene leads to the presence (ETV1 alpha) or the
      absence (ETV1 beta) of exon 5 encoding the C-terminal part of the transcriptional
      acidic domain, but without affecting the alpha helix previously described as
      crucial for transactivation. We demonstrated here that the truncated isoform
      (human ETV1 beta) and the full-length isoform (human ETV1 alpha) bind similarly
      specific DNA Ets binding sites. Moreover, they both activate transcription
      similarly through the PKA-transduction pathway, so suggesting that this
      alternative splicing is not crucial for the function of this protein as a
      transcription factor. The comparison of human ETV1 alpha and human ETV1 beta
      expression in the same tissues, such as the adrenal gland or the bladder, showed 
      no clear-cut differences. Altogether, these data open a new avenue of
      investigation leading to a better understanding of the functional role of this
      transcription factor.
FAU - Coutte, L
AU  - Coutte L
AD  - UMR 8526 CNRS, Institut Pasteur de Lille, France.
FAU - Monte, D
AU  - Monte D
FAU - Imai, K
AU  - Imai K
FAU - Pouilly, L
AU  - Pouilly L
FAU - Dewitte, F
AU  - Dewitte F
FAU - Vidaud, M
AU  - Vidaud M
FAU - Adamski, J
AU  - Adamski J
FAU - Baert, J L
AU  - Baert JL
FAU - de Launoit, Y
AU  - de Launoit Y
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ETV1 protein, human)
RN  - 0 (Etv1 protein, mouse)
RN  - 0 (Protein Isoforms)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Carcinoma/genetics/metabolism/pathology
MH  - Chromosome Mapping
MH  - DNA-Binding Proteins/biosynthesis/chemistry/*genetics
MH  - Exons/genetics
MH  - *Gene Expression Regulation
MH  - Gene Expression Regulation, Neoplastic
MH  - *Genes
MH  - Humans
MH  - Kidney Neoplasms/genetics/metabolism/pathology
MH  - Mice
MH  - Molecular Sequence Data
MH  - Organ Specificity
MH  - Protein Binding
MH  - Protein Isoforms/biosynthesis/chemistry/*genetics
MH  - Protein Structure, Tertiary
MH  - *RNA Splicing
MH  - Rabbits
MH  - Species Specificity
MH  - Transcription Factors/biosynthesis/chemistry/*genetics
MH  - Transcription, Genetic
MH  - Tumor Cells, Cultured
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1038/sj.onc.1203020 [doi]
PST - ppublish
SO  - Oncogene. 1999 Nov 4;18(46):6278-86. doi: 10.1038/sj.onc.1203020.