EWS differentially activates transcription of the Brn-3a long and short isoform mRNAs from distinct promoters.
Brn-3a long and short isoforms are known to be encoded by two distinct mRNA transcripts derived from a single gene. Here we report that transcription of the two isoforms is differentially regulated. The short isoform has its own promoter, though many elements in the 5' regulatory region are shared. The protein product of the EWS gene, translocations of which are associated with the Ewing's sarcoma family of tumours, is known to interact with Brn-3a via a direct protein-protein interaction. Here we show that EWS also regulates Brn-3a expression in an isoform-specific manner. The implications of these results are discussed in terms of the functional role of EWS and the distinct functional activities of the two isoforms of Brn-3a.
Thomas
G R
GR
Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
Faulkes
D J
DJ
Gascoyne
D
D
Latchman
D S
DS
D000818:Animals; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005796:Genes / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014176:Protein Biosynthesis; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D034802:RNA-Binding Protein EWS / Q000378:metabolism*; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C494189:Pou4f1 protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; D034802:RNA-Binding Protein EWS; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors; D008156:Luciferases