raf regulates the postnatal repression of the mouse alpha-fetoprotein gene at the posttranscriptional level.
The mouse alpha-fetoprotein (AFP) gene is transcribed at a high rate in liver during the second half of gestation. Its steady-state mRNA levels decrease 10(4)-fold shortly after birth, at least in part as the consequence of a dramatic decrease in its transcription rate. The final basal level of AFP mRNA in adult liver is influenced by a trans-acting locus on chromosome 15 termed raf. Two strategies were used to demonstrate that the raf gene acts posttranscriptionally to affect the processing and/or stability of AFP transcripts. Transgenic mouse studies demonstrated that raf gene action is independent of both positive and negative transcription control elements of the AFP gene. Nuclear run-on analysis was used to confirm that transcriptions of both AFP transgenes and another endogenous raf-responsive gene, H19, are invariant with respect to the raf genotype. Thus, the postnatal repression of the AFP gene is mediated by both transcriptional and posttranscriptional mechanisms.
Vacher
J
J
Howard Hughes Medical Institute, Princeton University, New Jersey 08544.
Camper
S A
SA
Krumlauf
R
R
Compton
R S
RS
Tilghman
S M
SM
D000418:Albumins / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000235:genetics*
D000418:Albumins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D000509:alpha-Fetoproteins; D019908:Proto-Oncogene Proteins c-raf