Transcriptional up-regulation of the delayed early gene HRS/SRp40 during liver regeneration. Interactions among YY1, GA-binding proteins, and mitogenic signals.
Arg-Ser-rich domain-containing proteins (SR proteins), a family of splicing factors, can regulate pre-mRNA alternative splicing in a concentration dependent manner. Thus, the relative expression of various SR proteins may play an important role in alternative splicing regulation. HRS/SRp40, an SR protein and delayed early gene in liver regeneration, can mediate alternative splicing of fibronectin mRNA. Here we determined that transcription of the HRS/SRp40 gene is induced about 5-fold during liver regeneration, similar to the level of steady-state mRNA. We found that both mouse and human HRS promoters lack TATA and CAAT boxes. The mouse promoter region from -130 to -18, which contains highly conserved GA-binding protein (GABP) and YY1 binding sites, conferred high transcriptional activity. While GABPalpha/GABPbeta heterodimer transactivated the HRS promoter, YY1 functioned as a repressor. During liver regeneration, the relative amount of GABPalpha/GABPbeta heterodimer increased 3-fold, and YY1 changed little, which could partially account for the increase in HRS gene transcription. Interleukin-6, a critical mitogenic component of liver regeneration, was able to relieve the repressive activity of the YY1 site within the HRS promoter. The combined effect of small changes in the level of existing transcription factors and mitogenic signals may explain the transcriptional activation of the HRS gene during cell growth.
Du
K
K
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Leu
J I
JI
Peng
Y
Y
Taub
R
R
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport; D050981:Erythroid-Specific DNA-Binding Factors; D051268:GA-Binding Protein Transcription Factor; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008115:Liver Regeneration / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis*; D010750:Phosphoproteins / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic / Q000235:genetics; D016601:RNA-Binding Proteins; D051381:Rats; D011916:Rats, Inbred F344; D017384:Sequence Deletion; D000068103:Serine-Arginine Splicing Factors; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation; D050986:YY1 Transcription Factor
C083058:C-EPB transcription factor; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D050981:Erythroid-Specific DNA-Binding Factors; D051268:GA-Binding Protein Transcription Factor; D015850:Interleukin-6; D008934:Mitogens; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C494699:Yy1 protein, mouse; C494700:Yy1 protein, rat; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate; D000068103:Serine-Arginine Splicing Factors