Transcription factor AP-2delta regulates the expression of polysialyltransferase ST8SIA2 in chick retina.
The AP-2δ transcription factor is restricted to a subset of retinal ganglion cells. Overexpression of AP-2δ in chick retina results in induction of polysialylated neural cell adhesion molecule (PSA-NCAM) accompanied by misrouting and bundling of ganglion cell axons. Two polysialyltransferases, ST8SIA2 and ST8SIA4, are responsible for polysialylation of NCAM. Here, we investigate the mechanism driving the increase in PSA-NCAM observed upon AP-2δ overexpression. We show that ST8SIA2 is induced by AP-2δ overexpression in chick retina. We use chromatin immunoprecipitation and gel shift assays to demonstrate direct interaction between AP-2δ and the ST8SIA2 promoter. We propose that up-regulation of ST8SIA2 upon AP-2δ overexpression in retina increases ectopic polysialylation of NCAM which in turn causes premature bundling of axons and alters axonal response to guidance cues.
Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada.
Xiaodong
X
Li
Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada.
Amit R L
AR
Persad
Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada.
Elizabeth A
EA
Monckton
Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada. Electronic address: rgodbout@ualberta.ca.
Roseline
R
Godbout
D000818:Animals; D030161:Avian Proteins / Q000235:genetics* / Q000378:metabolism; D001369:Axons / Q000201:enzymology; D001483:Base Sequence; D001665:Binding Sites; D002642:Chick Embryo; D015971:Gene Expression Regulation, Enzymologic; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012160:Retina / Q000166:cytology / Q000201:enzymology*; D012165:Retinal Ganglion Cells / Q000201:enzymology; D012799:Sialyltransferases / Q000235:genetics* / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000502:physiology*
D030161:Avian Proteins; D050656:Transcription Factor AP-2; D012799:Sialyltransferases
Chromatin immunoprecipitation; Gel shift; PSA-NCAM; Polysialyltransferase; Retina; ST8SIA2