TY - JOUR
T1 - The transcription factor GTF2IRD1 regulates the topology and function of photoreceptors by modulating photoreceptor gene expression across the retina
AU - Masuda, Xtomohiro
AU - Zhang, Xiaodong
AU - Berlinicke, Cindy
AU - Wan, Jun
AU - Yerrabelli, Anitha
AU - Conner, Elizabeth A.
AU - Kjellstrom, Sten
AU - Bush, Ronald
AU - Thorgeirsson, Snorri S.
AU - Swaroop, Anand
AU - Chen, Shiming
AU - Zack, Donald J.
N1 - Publisher Copyright:
© 2014 the authors.
PY - 2014/11/12
Y1 - 2014/11/12
N2 - 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.
AB - 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.
KW - Gene expression
KW - Opsin
KW - Photoreceptor
KW - Retina
KW - Transcription factor
UR - http://www.scopus.com/inward/record.url?scp=84909972090&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2089-14.2014
DO - 10.1523/JNEUROSCI.2089-14.2014
M3 - Article
C2 - 25392503
AN - SCOPUS:84909972090
SN - 0270-6474
VL - 34
SP - 15356
EP - 15368
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 46
ER -