Genetic elements regulating HES-1 induction in Wnt-1-transformed PC12 cells.
PC12 cells differentiate in response to nerve growth factor from a chromaffin cell to a sympathetic neuronal phenotype. Wnt-1 is a secreted signaling factor required for development of mammalian midbrain and cerebellum. PC12 cells transformed by Wnt-1 fail to express several differentiation-specific genes in response to nerve growth factor. We have previously shown that HES-1, a negative regulator of neuronal differentiation, is increased in Wnt-1/PC12 cells (P. S. Issack and E. B. Ziff. Altered expression of helix-loop-helix transcriptional regulators and cyclin D1 in Wnt-1-transformed PC12 cells. Cell Growth & Differ., 9: 837-845). Here, we show that the HES-1 promoter is more active in Wnt-1/PC12 cells relative to PC12 and that the binding sites for the transcription factor RBP-J kappa contribute to this induction. We also identify two additional promoter elements required for elevated HES-1 expression. One element binds Wnt-1-induced protein complexes in a sequence-specific manner. Identification of Wnt-1 responsive elements in potential target genes may provide clues to nuclear pathways regulated by Wnt-1.
Issack
P S
PS
Howard Hughes Medical Institute, Department of Biochemistry and Kaplan Cancer Center, New York University Medical Center, New York 10016, USA.
Ziff
E B
EB
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D018398:Homeodomain Proteins / Q000235:genetics*; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins; D016716:PC12 Cells; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D051381:Rats; D017384:Sequence Deletion; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000378:metabolism; D014170:Transformation, Genetic; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; C489735:Hes1 protein, rat; C497572:Rbpjl2 protein, rat; C495245:Wnt1 protein, rat