The transcription factor GTF2IRD1 regulates the topology and function of photoreceptors by modulating photoreceptor gene expression across the retina
(2014) In The Journal of Neuroscience : the official journal of the Society for Neuroscience 34(46). p.68-15356- Abstract
The mechanisms that specify photoreceptor cell-fate determination, especially as regards to short-wave-sensitive (S) versus medium-wave-sensitive (M) cone identity, and maintain their nature and function, are not fully understood. Here we report the importance of general transcription factor II-I repeat domain-containing protein 1 (GTF2IRD1) in maintaining M cone cell identity and function as well as rod function. In the mouse, GTF2IRD1 is expressed in cell-fate determined photoreceptors at postnatal day 10. GTF2IRD1 binds to enhancer and promoter regions in the mouse rhodopsin, M- and S-opsin genes, but regulates their expression differentially. Through interaction with the transcription factors CRX and thyroid hormone receptor β 2, it... (More)
The mechanisms that specify photoreceptor cell-fate determination, especially as regards to short-wave-sensitive (S) versus medium-wave-sensitive (M) cone identity, and maintain their nature and function, are not fully understood. Here we report the importance of general transcription factor II-I repeat domain-containing protein 1 (GTF2IRD1) in maintaining M cone cell identity and function as well as rod function. In the mouse, GTF2IRD1 is expressed in cell-fate determined photoreceptors at postnatal day 10. GTF2IRD1 binds to enhancer and promoter regions in the mouse rhodopsin, M- and S-opsin genes, but regulates their expression differentially. Through interaction with the transcription factors CRX and thyroid hormone receptor β 2, it enhances M-opsin expression, whereas it suppresses S-opsin expression; and with CRX and NRL, it enhances rhodopsin expression. In an apparent paradox, although GTF2IRD1 is widely expressed in multiple cell types across the retina, knock-out of GTF2IRD1 alters the retinal expression of only a limited number of annotated genes. Interestingly, however, the null mutation leads to altered topology of cone opsin expression in the retina, with aberrant S-opsin overexpression and M-opsin underexpression in M cones. Gtf2ird1-null mice also demonstrate abnormal M cone and rod electrophysiological responses. These findings suggest an important role for GTF2IRD1 in regulating the level and topology of rod and cone gene expression, and in maintaining normal retinal function.
(Less)
- author
- publishing date
- 2014-11-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Animals, Basic-Leucine Zipper Transcription Factors, Electroretinography, Eye Proteins, Gene Expression Regulation, Homeodomain Proteins, Mice, Mice, Knockout, Muscle Proteins, Nuclear Proteins, Opsins, Primary Cell Culture, Retina, Retinal Cone Photoreceptor Cells, Retinal Rod Photoreceptor Cells, Rhodopsin, Thyroid Hormone Receptors beta, Trans-Activators, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
- in
- The Journal of Neuroscience : the official journal of the Society for Neuroscience
- volume
- 34
- issue
- 46
- pages
- 13 pages
- publisher
- Society for Neuroscience
- external identifiers
-
- scopus:84909972090
- pmid:25392503
- ISSN
- 1529-2401
- DOI
- 10.1523/JNEUROSCI.2089-14.2014
- language
- English
- LU publication?
- no
- id
- e1233a52-5beb-4bcf-9e26-2c0539c90d1c
- date added to LUP
- 2017-04-14 08:26:09
- date last changed
- 2024-05-12 12:00:21
@article{e1233a52-5beb-4bcf-9e26-2c0539c90d1c,
abstract = {{<p>The mechanisms that specify photoreceptor cell-fate determination, especially as regards to short-wave-sensitive (S) versus medium-wave-sensitive (M) cone identity, and maintain their nature and function, are not fully understood. Here we report the importance of general transcription factor II-I repeat domain-containing protein 1 (GTF2IRD1) in maintaining M cone cell identity and function as well as rod function. In the mouse, GTF2IRD1 is expressed in cell-fate determined photoreceptors at postnatal day 10. GTF2IRD1 binds to enhancer and promoter regions in the mouse rhodopsin, M- and S-opsin genes, but regulates their expression differentially. Through interaction with the transcription factors CRX and thyroid hormone receptor β 2, it enhances M-opsin expression, whereas it suppresses S-opsin expression; and with CRX and NRL, it enhances rhodopsin expression. In an apparent paradox, although GTF2IRD1 is widely expressed in multiple cell types across the retina, knock-out of GTF2IRD1 alters the retinal expression of only a limited number of annotated genes. Interestingly, however, the null mutation leads to altered topology of cone opsin expression in the retina, with aberrant S-opsin overexpression and M-opsin underexpression in M cones. Gtf2ird1-null mice also demonstrate abnormal M cone and rod electrophysiological responses. These findings suggest an important role for GTF2IRD1 in regulating the level and topology of rod and cone gene expression, and in maintaining normal retinal function.</p>}},
author = {{Masuda, Tomohiro and Zhang, Xiaodong and Berlinicke, Cindy and Wan, Jun and Yerrabelli, Anitha and Conner, Elizabeth A and Kjellstrom, Sten and Bush, Ronald A and Thorgeirsson, Snorri S and Swaroop, Anand and Chen, Shiming and Zack, Donald J.}},
issn = {{1529-2401}},
keywords = {{Animals; Basic-Leucine Zipper Transcription Factors; Electroretinography; Eye Proteins; Gene Expression Regulation; Homeodomain Proteins; Mice; Mice, Knockout; Muscle Proteins; Nuclear Proteins; Opsins; Primary Cell Culture; Retina; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Rhodopsin; Thyroid Hormone Receptors beta; Trans-Activators; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}},
language = {{eng}},
month = {{11}},
number = {{46}},
pages = {{68--15356}},
publisher = {{Society for Neuroscience}},
series = {{The Journal of Neuroscience : the official journal of the Society for Neuroscience}},
title = {{The transcription factor GTF2IRD1 regulates the topology and function of photoreceptors by modulating photoreceptor gene expression across the retina}},
url = {{http://dx.doi.org/10.1523/JNEUROSCI.2089-14.2014}},
doi = {{10.1523/JNEUROSCI.2089-14.2014}},
volume = {{34}},
year = {{2014}},
}