A novel fibroblast growth factor gene expressed in the developing nervous system is a downstream target of the chimeric homeodomain oncoprotein E2A-Pbx1.
Pbx1 is a homeodomain transcription factor that has the ability to form heterodimers with homeodomain proteins encoded by the homeotic selector (Hox) gene complexes and increase their DNA-binding affinity and specificity. A current hypothesis proposes that interactions with Pbx1 are necessary for Hox proteins to regulate downstream target genes that in turn control growth, differentiation and morphogenesis during development. In pre B cell leukemias containing the t(1;19) chromosome translocation, Pbx1 is converted into a strong transactivator by fusion to the activation domain of the bHLH transcription factor E2A. The E2A-Pbx1 fusion protein should therefore activate transcription of genes normally regulated by Pbx1. We have used the subtractive process of representational difference analysis to identify targets of E2A-Pbx1. We show that E2A-Pbx1 can directly activate transcription of a novel member of the fibroblast growth factor family of intercellular signalling molecules, FGF-15. The FGF-15 gene is expressed in a regionally restricted pattern in the developing nervous system, suggesting that FGF-15 may play an important role in regulating cell division and patterning within specific regions of the embryonic brain, spinal cord and sensory organs.
McWhirter
J R
JR
Department of Biology, School of Medicine, University of California, San Diego, La Jolla 92093, USA.
Goulding
M
M
Weiner
J A
JA
Chun
J
J
Murre
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002490:Central Nervous System / Q000196:embryology* / Q000254:growth & development*; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D017386:Sequence Homology, Amino Acid; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism; D015533:Transcriptional Activation
D017931:DNA Primers; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D015514:Oncogene Proteins, Fusion; C108526:fibroblast growth factor 15, mouse; C089847:E2A-Pbx1 fusion protein; D005346:Fibroblast Growth Factors