Pias3-Dependent SUMOylation Directs Rod Photoreceptor Development

Akishi Onishi; Guang Hua Peng; Chengda Hsu; Uel Alexis; Shiming Chen; Seth Blackshaw

doi:10.1016/j.neuron.2008.12.006

Pias3-Dependent SUMOylation Directs Rod Photoreceptor Development

Akishi Onishi, Guang Hua Peng, Chengda Hsu, Uel Alexis, Shiming Chen, Seth Blackshaw

School of Medicine

Research output: Contribution to journal › Article › peer-review

92 Scopus citations

Abstract

Specification of retinal rod photoreceptors is determined by several different transcription factors that activate expression of rod-specific genes and repress expression of cone photoreceptor-specific genes. The mechanism by which this dual regulation occurs is unclear. We have found that Pias3, a transcriptional coregulator and E3 SUMO ligase that is selectively expressed in developing photoreceptors, promotes the differentiation of rod photoreceptors while preventing rods from adopting cone photoreceptor-like characteristics. Pias3 binds the photoreceptor-specific transcription factors Crx and Nr2e3 and is specifically targeted to the promoters of photoreceptor-specific genes. Pias3 SUMOylates Nr2e3, converting it into a potent repressor of cone-specific gene expression. Rod- and cone-specific promoters are bound by hyperSUMOylated proteins in rod photoreceptors, and blocking SUMOylation in photoreceptors results in cells with morphological and molecular features of cones and an absence of rod-specific markers. Our data thus identify Pias3-mediated SUMOylation of photoreceptor-specific transcription factors as a key mechanism of rod specification.

Original language	English (US)
Pages (from-to)	234-246
Number of pages	13
Journal	Neuron
Volume	61
Issue number	2
DOIs	https://doi.org/10.1016/j.neuron.2008.12.006
State	Published - Jan 29 2009

Keywords

DEVBIO
MOLNEURO
SIGNALING

ASJC Scopus subject areas

General Neuroscience

Access to Document

10.1016/j.neuron.2008.12.006

Cite this

@article{619adb34d15845e0a567140dc3b2b0ee,

title = "Pias3-Dependent SUMOylation Directs Rod Photoreceptor Development",

abstract = "Specification of retinal rod photoreceptors is determined by several different transcription factors that activate expression of rod-specific genes and repress expression of cone photoreceptor-specific genes. The mechanism by which this dual regulation occurs is unclear. We have found that Pias3, a transcriptional coregulator and E3 SUMO ligase that is selectively expressed in developing photoreceptors, promotes the differentiation of rod photoreceptors while preventing rods from adopting cone photoreceptor-like characteristics. Pias3 binds the photoreceptor-specific transcription factors Crx and Nr2e3 and is specifically targeted to the promoters of photoreceptor-specific genes. Pias3 SUMOylates Nr2e3, converting it into a potent repressor of cone-specific gene expression. Rod- and cone-specific promoters are bound by hyperSUMOylated proteins in rod photoreceptors, and blocking SUMOylation in photoreceptors results in cells with morphological and molecular features of cones and an absence of rod-specific markers. Our data thus identify Pias3-mediated SUMOylation of photoreceptor-specific transcription factors as a key mechanism of rod specification.",

keywords = "DEVBIO, MOLNEURO, SIGNALING",

author = "Akishi Onishi and Peng, {Guang Hua} and Chengda Hsu and Uel Alexis and Shiming Chen and Seth Blackshaw",

note = "Funding Information: We thank Tomomi Shimogori, Heng Zhu, Jef Boeke, Jeremy Nathans, Don Zack, and Geraldine Seydoux for comments on the manuscript; Connie Cepko for the Crx −/− mice; Eliazer Kopf, Douglas Forrest, and Michael Matunis for antibodies; Ke Shuai, Fang Liu, and Albert La Spada for plasmids; and Anne Hennig, Hui Wang, and Belinda McMahan for technical assistance. This work was supported by R01EY017015, an Alfred P. Sloan Young Investigator Award, and a W.M. Keck Distinguished Young Scholar in Medical Research Award (to S.B.), research fellowships from the Japan Society for the Promotion of Science for Young Scientists (to A.O.), R01 EY012543 (to S.C.), EY02687 and Research to Prevent Blindness (to WU-DOVS). ",

year = "2009",

month = jan,

day = "29",

doi = "10.1016/j.neuron.2008.12.006",

language = "English (US)",

volume = "61",

pages = "234--246",

journal = "Neuron",

issn = "0896-6273",

publisher = "Cell Press",

number = "2",

}

TY - JOUR

T1 - Pias3-Dependent SUMOylation Directs Rod Photoreceptor Development

AU - Onishi, Akishi

AU - Peng, Guang Hua

AU - Hsu, Chengda

AU - Alexis, Uel

AU - Chen, Shiming

AU - Blackshaw, Seth

N1 - Funding Information: We thank Tomomi Shimogori, Heng Zhu, Jef Boeke, Jeremy Nathans, Don Zack, and Geraldine Seydoux for comments on the manuscript; Connie Cepko for the Crx −/− mice; Eliazer Kopf, Douglas Forrest, and Michael Matunis for antibodies; Ke Shuai, Fang Liu, and Albert La Spada for plasmids; and Anne Hennig, Hui Wang, and Belinda McMahan for technical assistance. This work was supported by R01EY017015, an Alfred P. Sloan Young Investigator Award, and a W.M. Keck Distinguished Young Scholar in Medical Research Award (to S.B.), research fellowships from the Japan Society for the Promotion of Science for Young Scientists (to A.O.), R01 EY012543 (to S.C.), EY02687 and Research to Prevent Blindness (to WU-DOVS).

PY - 2009/1/29

Y1 - 2009/1/29

N2 - Specification of retinal rod photoreceptors is determined by several different transcription factors that activate expression of rod-specific genes and repress expression of cone photoreceptor-specific genes. The mechanism by which this dual regulation occurs is unclear. We have found that Pias3, a transcriptional coregulator and E3 SUMO ligase that is selectively expressed in developing photoreceptors, promotes the differentiation of rod photoreceptors while preventing rods from adopting cone photoreceptor-like characteristics. Pias3 binds the photoreceptor-specific transcription factors Crx and Nr2e3 and is specifically targeted to the promoters of photoreceptor-specific genes. Pias3 SUMOylates Nr2e3, converting it into a potent repressor of cone-specific gene expression. Rod- and cone-specific promoters are bound by hyperSUMOylated proteins in rod photoreceptors, and blocking SUMOylation in photoreceptors results in cells with morphological and molecular features of cones and an absence of rod-specific markers. Our data thus identify Pias3-mediated SUMOylation of photoreceptor-specific transcription factors as a key mechanism of rod specification.

AB - Specification of retinal rod photoreceptors is determined by several different transcription factors that activate expression of rod-specific genes and repress expression of cone photoreceptor-specific genes. The mechanism by which this dual regulation occurs is unclear. We have found that Pias3, a transcriptional coregulator and E3 SUMO ligase that is selectively expressed in developing photoreceptors, promotes the differentiation of rod photoreceptors while preventing rods from adopting cone photoreceptor-like characteristics. Pias3 binds the photoreceptor-specific transcription factors Crx and Nr2e3 and is specifically targeted to the promoters of photoreceptor-specific genes. Pias3 SUMOylates Nr2e3, converting it into a potent repressor of cone-specific gene expression. Rod- and cone-specific promoters are bound by hyperSUMOylated proteins in rod photoreceptors, and blocking SUMOylation in photoreceptors results in cells with morphological and molecular features of cones and an absence of rod-specific markers. Our data thus identify Pias3-mediated SUMOylation of photoreceptor-specific transcription factors as a key mechanism of rod specification.

KW - DEVBIO

KW - MOLNEURO

KW - SIGNALING

UR - http://www.scopus.com/inward/record.url?scp=58549108816&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58549108816&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2008.12.006

DO - 10.1016/j.neuron.2008.12.006

M3 - Article

C2 - 19186166

AN - SCOPUS:58549108816

SN - 0896-6273

VL - 61

SP - 234

EP - 246

JO - Neuron

JF - Neuron

IS - 2

ER -

Pias3-Dependent SUMOylation Directs Rod Photoreceptor Development

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this