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.
Howard Hughes Medical Institute, Princeton University, New Jersey 08544.
J
J
Vacher
S A
SA
Camper
R
R
Krumlauf
R S
RS
Compton
S M
SM
Tilghman
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