Modulation of DNA binding specificity by alternative splicing of the Wilms tumor wt1 gene transcript.
The technique of whole-genome polymerase chain reaction was used to study the DNA binding properties of the product of the wt1 gene. The zinc finger region of this gene is alternatively spliced such that the major transcript encodes a protein with three extra amino acids between the third and fourth fingers. The minor form of the protein binds specifically to DNA. It is now shown that the major form of wt1 messenger RNA encodes a protein that binds to DNA with a specificity that differs from that of the minor form. Therefore, alternative splicing within the DNA binding domain of a transcription factor can generate proteins with distinct DNA binding specificities and probably different physiological targets.
Bickmore
W A
WA
Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh, Scotland.
Oghene
K
K
Little
M H
MH
Seawright
A
A
van Heyningen
V
V
Hastie
N D
ND
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics*; D001667:Binding, Competitive; D002880:Chromosomes, Human, Pair 11; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D025721:WT1 Proteins; D009396:Wilms Tumor / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D025721:WT1 Proteins; D004247:DNA