Nr2e3-directed transcriptional regulation of genes involved in photoreceptor development and cell-type specific phototransduction

被引：72

作者：

Haider, Neena B. ^{[1
,2
]}

Mollema, Nissa ^{[1
]}

Gaule, Meghan ^{[1
]}

Yuan, Yang ^{[1
]}

Sachs, Andrew J. ^{[1
]}

Nystuen, Arne M. ^{[1
]}

Naggert, Juergen K. ^{[3
]}

Nishina, Patsy M. ^{[3
]}

机构：

[1] Univ Nebraska Med Ctr, Dept Genet Cell Biol & Anat, Omaha, NE 68198 USA

[2] Univ Nebraska Med Ctr, Dept Ophthalmol & Visual Sci, Omaha, NE 68198 USA

[3] Jackson Lab, Bar Harbor, ME 04609 USA

来源：

EXPERIMENTAL EYE RESEARCH | 2009年 / 89卷 / 03期

关键词：

retina; Nr2e3; gene expression; Enhanced-S-cone syndrome; rd7; development; phototransduction; retinitis pigmentosa; NUCLEAR RECEPTOR NR2E3; S-CONE-SYNDROME; CAUSES RETINAL DEGENERATION; MUTATION; ROD; CRX; DIFFERENTIATION; IDENTIFICATION; EXPRESSION; SUPPRESS;

D O I：

10.1016/j.exer.2009.04.006

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

The retinal transcription factor Nr2e3 plays a key role in photoreceptor development and function. In this study we examine gene expression in the retina of Nr2e3(rd7/rd7) mutants with respect to wild-type control mice, to identify genes that are misregulated and hence potentially function in the Nr2e3 transcriptional network. Quantitative candidate gene real time PCR and subtractive hybridization approaches were used to identify transcripts that were misregulated in Nr2e3(rd7/rd7) mice. Chromatin immunoprecipitation assays were then used to determine which of the misregulated transcripts were direct targets of NR2E3. We identified 24 potential targets of NR2E3. In the developing retina, NR2E3 targets transcription factors such as Ror1, Rorg, and the nuclear hormone receptors Nr1d1 and Nr2c1. In the mature retina NR2E3 targets several genes including the rod specific gene Gnb1 and cone specific genes blue opsin, and two of the cone transducin subunits, Gnat2 and Gnb3. In addition, we identified 5 novel transcripts that are targeted by NR2E3. While mislocalization of proteins between rods and cones was not observed, we did observe diminished concentration of GNB1 protein in adult Nr2e3(rd7/rd7) retinas. These studies identified novel transcriptional pathways that are potentially targeted by Nr2e3 in the retina and specifically demonstrate a novel role for NR2E3 in regulating genes involved in phototransduction. (c) 2009 Elsevier Ltd. All rights reserved.

引用

页码：365 / 372

页数：8

共 37 条

[1] A deletion in a photoreceptor-specific nuclear receptor mRNA causes retinal degeneration in the rd7 mouse [J].

Akhmedov, NB ;

Piriev, NI ;

Chang, B ;

Rapoport, AL ;

Hawes, NL ;

Nishina, PM ;

Nusinowitz, S ;

Heckenlively, JR ;

Roderick, TH ;

Kozak, CA ;

Danciger, M ;

Davisson, MT ;

Farber, DB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (10) :5551-5556

[2] An Arg311Gln NR2E3 mutation in a family with classic Goldmann-Favre syndrome [J].

Chavala, SH ;

Sari, A ;

Lewis, H ;

Pauer, GJT ;

Simpson, E ;

Hagstrom, SA ;

Traboulsi, EI .

BRITISH JOURNAL OF OPHTHALMOLOGY, 2005, 89 (08) :1065-1066

[3] The rod photoreceptor-specific nuclear receptor Nr2e3 represses transcription of multiple cone-specific genes [J].

Chen, JC ;

Rattner, A ;

Nathans, J .

JOURNAL OF NEUROSCIENCE, 2005, 25 (01) :118-129

[4] Photoreceptor-specific nuclear receptor NR2E3 functions as a transcriptional activator in rod photoreceptors [J].

Cheng, H ;

Khanna, H ;

Oh, ECT ;

Hicks, D ;

Mitton, KP ;

Swaroop, A .

HUMAN MOLECULAR GENETICS, 2004, 13 (15) :1563-1575

[5] In vivo function of the orphan nuclear receptor NR2E3 in establishing photoreceptor identity during mammalian retinal development [J].

Cheng, Hong ;

Aleman, Tomas S. ;

Cideciyan, Artur V. ;

Khanna, Ritu ;

Jacobson, Samuel G. ;

Swaroop, Anand .

HUMAN MOLECULAR GENETICS, 2006, 15 (17) :2588-2602

[6] Recurrent mutation in the first zinc finger of the orphan nuclear receptor NR2E3 causes autosomal dominant retinitis pigmentosa [J].

Coppieters, Frauke ;

Leroy, Bart P. ;

Beysen, Diane ;

Hellemans, Jan ;

De Bosscher, Karolien ;

Haegeman, Guy ;

Robberecht, Kirsten ;

Wuyts, Wim ;

Coucke, Paul J. ;

De Baere, Elfride .

AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 81 (01) :147-157

[7] A hybrid photoreceptor expressing both rod and cone genes in a mouse model of enhanced S-cone syndrome [J].

Corbo, JC ;

Cepko, CL .

PLOS GENETICS, 2005, 1 (02) :140-153

[8]

FAVRE M, 1958, Ophthalmologica, V135, P604

[9] DIAGNOSTIC FEATURES OF FAVRE-GOLDMANN SYNDROME [J].

FISHMAN, GA ;

JAMPOL, LM ;

GOLDBERG, MF .

BRITISH JOURNAL OF OPHTHALMOLOGY, 1976, 60 (05) :345-353

[10] The photoreceptor cell-specific nuclear receptor gene (PNR) accounts for retinitis pigmentosa in the Crypto-Jews from Portugal (Marranos), survivors from the Spanish Inquisition [J].

Gerber, S ;

Rozet, JM ;

Takezawa, SI ;

dos Santos, LC ;

Lopes, L ;

Gribouval, O ;

Penet, C ;

Perrault, I ;

Ducroq, D ;

Souied, E ;

Jeanpierre, M ;

Romana, S ;

Frézal, J ;

Ferraz, F ;

Yu-Umesono, R ;

Munnich, A ;

Kaplan, J .

HUMAN GENETICS, 2000, 107 (03) :276-284

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