TY - JOUR
T1 - Pax6 Regulates Gene Expression in the Vertebrate Lens through miR-204
AU - Shaham, Ohad
AU - Gueta, Karen
AU - Mor, Eyal
AU - Oren-Giladi, Pazit
AU - Grinberg, Dina
AU - Xie, Qing
AU - Cvekl, Ales
AU - Shomron, Noam
AU - Davis, Noa
AU - Keydar-Prizant, Maya
AU - Raviv, Shaul
AU - Pasmanik-Chor, Metsada
AU - Bell, Rachel E.
AU - Levy, Carmit
AU - Avellino, Raffaella
AU - Banfi, Sandro
AU - Conte, Ivan
AU - Ashery-Padan, Ruth
PY - 2013
Y1 - 2013
N2 - During development, tissue-specific transcription factors regulate both protein-coding and non-coding genes to control differentiation. Recent studies have established a dual role for the transcription factor Pax6 as both an activator and repressor of gene expression in the eye, central nervous system, and pancreas. However, the molecular mechanism underlying the inhibitory activity of Pax6 is not fully understood. Here, we reveal that Trpm3 and the intronic microRNA gene miR-204 are co-regulated by Pax6 during eye development. miR-204 is probably the best known microRNA to function as a negative modulator of gene expression during eye development in vertebrates. Analysis of genes altered in mouse Pax6 mutants during lens development revealed significant over-representation of miR-204 targets among the genes up-regulated in the Pax6 mutant lens. A number of new targets of miR-204 were revealed, among them Sox11, a member of the SoxC family of pro-neuronal transcription factors, and an important regulator of eye development. Expression of Trpm/miR-204 and a few of its targets are also Pax6-dependent in medaka fish eyes. Collectively, this study identifies a novel evolutionarily conserved mechanism by which Pax6 controls the down-regulation of multiple genes through direct up-regulation of miR-204.
AB - During development, tissue-specific transcription factors regulate both protein-coding and non-coding genes to control differentiation. Recent studies have established a dual role for the transcription factor Pax6 as both an activator and repressor of gene expression in the eye, central nervous system, and pancreas. However, the molecular mechanism underlying the inhibitory activity of Pax6 is not fully understood. Here, we reveal that Trpm3 and the intronic microRNA gene miR-204 are co-regulated by Pax6 during eye development. miR-204 is probably the best known microRNA to function as a negative modulator of gene expression during eye development in vertebrates. Analysis of genes altered in mouse Pax6 mutants during lens development revealed significant over-representation of miR-204 targets among the genes up-regulated in the Pax6 mutant lens. A number of new targets of miR-204 were revealed, among them Sox11, a member of the SoxC family of pro-neuronal transcription factors, and an important regulator of eye development. Expression of Trpm/miR-204 and a few of its targets are also Pax6-dependent in medaka fish eyes. Collectively, this study identifies a novel evolutionarily conserved mechanism by which Pax6 controls the down-regulation of multiple genes through direct up-regulation of miR-204.
UR - http://www.scopus.com/inward/record.url?scp=84875981176&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.1003357
DO - 10.1371/journal.pgen.1003357
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 23516376
AN - SCOPUS:84875981176
SN - 1553-7390
VL - 9
JO - PLoS Genetics
JF - PLoS Genetics
IS - 3
M1 - e1003357
ER -
