Hostname: page-component-745bb68f8f-kw2vx Total loading time: 0 Render date: 2025-01-11T10:36:05.090Z Has data issue: false hasContentIssue false
  • English
  • Français

Chromatin immunoprecipitation identifies photoreceptor transcription factor targets in mouse models of retinal degeneration: New findings and challenges

Published online by Cambridge University Press:  06 December 2005

GUANG-HUA PENG  and
SHIMING CHEN
GUANG-HUA PENG
Affiliation:
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis
SHIMING CHEN
Affiliation:
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis
Get access Rights & Permissions [Opens in a new window]

Abstract

The transcription factors, Otx2, Crx, Nrl, and Nr2e3, expressed by retinal photoreceptor cells are essential for photoreceptor gene expression, development, and maintenance. Malfunction of any of these factors due to genetic mutations causes photoreceptor disease. Protein–protein interaction studies suggest that these factors may form a regulatory network centered on Crx. To understand how these factors regulate photoreceptor gene transcription in vivo, we have employed chromatin immunoprecipitation (ChIP) assays to assess the ability of these proteins to bind to regulatory sequences of photoreceptor genes in the retina of wild-type and mutant mice with photoreceptor degeneration. This paper summarizes the advantages and limitations of ChIP, using examples from our studies to demonstrate how this technique has contributed to our understanding of the regulation of photoreceptor gene expression. We report that Crx, Otx2, Nrl, and Nr2e3 co-occupy the promoter/enhancer, but not the region 3′ of selected Crx target genes, in a retina-specific fashion. We identified Crx-dependent (Nr2e3) and Crx-independent (Otx2 and Nrl) target binding using Crx knockout mice (Crx−/−), suggesting that individual factors may use distinct mechanism(s) for binding and regulating target genes. Consistent with ChIP results, we also found that Otx2, a close family member of Crx, can activate the promoter of rod and cone genes in HEK293 cells, implicating Otx2 in regulating photoreceptor gene expression. These findings provide important information for understanding how photoreceptor transcription factors regulate photoreceptor gene expression and the mechanisms by which mutations in these factors cause transcriptional dysregulation and photoreceptor degeneration.

Keywords

Photoreceptor transcription factorsTargetsChromatin immunoprecipitationRetinal degeneration
Type
Research Article
Information
Visual Neuroscience , Volume 22 , Issue 5 , September 2005 , pp. 575 - 586
Copyright
© 2005 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Acampora, D., Mazan, S., Lallemand, Y., Avantaggiato, V., Maury, M., Simeone, A., & Brulet, P. (1995). Forebrain and midbrain regions are deleted in Otx2−/− mutants due to a defective anterior neuroectoderm specification during gastrulation. Development 121, 3279–3290.Google Scholar
Akhmedov, N.B., Piriev, N.I., Chang, B., Rapoport, A.L., Hawes, N.L., Nishina, P.M., Nusinowitz, S., Heckenlively, J.R., Roderick, T.H., Kozak, C.A., Danciger, M., Davisson, M.T., & Farber, D.B. (2000). A deletion in a photoreceptor-specific nuclear receptor mRNA causes retinal degeneration in the rd7 mouse. Proceedings of the National Academy of Sciences of the U.S.A. 97, 5551–5556.CrossRefGoogle Scholar
al-Ubaidi, M.R., Font, R.L., Quiambao, A.B., Keener, M.J., Liou, G.I., Overbeek, P.A., & Baehr, W. (1992). Bilateral retinal and brain tumors in transgenic mice expressing simian virus 40 large T antigen under control of the human interphotoreceptor retinoid-binding protein promoter. Journal of Cell Biology 119, 1681–1687.CrossRefGoogle Scholar
Ang, S.L., Jin, O., Rhinn, M., Daigle, N., Stevenson, L., & Rossant, J. (1996). A targeted mouse Otx2 mutation leads to severe defects in gastrulation and formation of axial mesoderm and to deletion of rostral brain. Development 122, 243–252.Google Scholar
Baas, D., Bumsted, K.M., Martinez, J.A., Vaccarino, F.M., Wikler, K.C., & Barnstable, C.J. (2000). The subcellular localization of Otx2 is cell-type specific and developmentally regulated in the mouse retina. Brain Research Molecular Brain Research 78, 26–37.CrossRefGoogle Scholar
Blackshaw, S., Fraioli, R.E., Furukawa, T., & Cepko, C.L. (2001). Comprehensive analysis of photoreceptor gene expression and the identification of candidate retinal disease genes. Cell 107, 579–589.CrossRefGoogle Scholar
Bobola, N., Briata, P., Ilengo, C., Rosatto, N., Craft, C., Corte, G., & Ravazzolo, R. (1999). OTX2 homeodomain protein binds a DNA element necessary for interphotoreceptor retinoid binding protein gene expression. Mechanisms of Development 82, 165–169.CrossRefGoogle Scholar
Bovolenta, P., Mallamaci, A., Briata, P., Corte, G., & Boncinelli, E. (1997). Implication of OTX2 in pigment epithelium determination and neural retina differentiation. Journal of Neuroscience 17, 4243–4252.Google Scholar
Bowes, C., Li, T., Danciger, M., Baxter, L.C., Applebury, M.L., & Farber, D.B. (1990). Retinal degeneration in the rd mouse is caused by a defect in the beta subunit of rod cGMP-phosphodiesterase. Nature 347, 677–680.CrossRefGoogle Scholar
Briata, P., Ilengo, C., Bobola, N., & Corte, G. (1999). Binding properties of the human homeodomain protein OTX2 to a DNA target sequence. FEBS Letters 445, 160–164.CrossRefGoogle Scholar
Bridges, C.D., Foster, R.G., Landers, R.A., & Fong, S.L. (1987). Interstitial retinol-binding protein and cellular retinal-binding protein in the mammalian pineal. Vision Research 27, 2049–2060.CrossRefGoogle Scholar
Carter-Dawson, L.D., LaVail, M.M., & Sidman, R.L. (1978). Differential effect of the rd mutation on rods and cones in the mouse retina. Investigative Ophthalmology and Visual Science 17, 489–498.Google Scholar
Cawley, S., Bekiranov, S., Ng, H.H., Kapranov, P., Sekinger, E.A., Kampa, D., Piccolboni, A., Sementchenko, V., Cheng, J., Williams, A.J., Wheeler, R., Wong, B., Drenkow, J., Yamanaka, M., Patel, S., Brubaker, S., Tammana, H., Helt, G., Struhl, K., & Gingeras, T.R. (2004). Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 116, 499–509.CrossRefGoogle Scholar
Chen, S., Peng, G.H., Wang, X., Smith, A.C., Grote, S.K., Sopher, B.L., & La Spada, A.R. (2004). Interference of Crx-dependent transcription by ataxin-7 involves interaction between the glutamine regions and requires the ataxin-7 carboxy-terminal region for nuclear localization. Human Molecular Genetics 13, 53–67.Google Scholar
Chen, S., Wang, Q.-L., Nie, Z., Sun, H., Lennon, G., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., & Zack, D.J. (1997). Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes. Neuron 19, 1017–1030.CrossRefGoogle Scholar
Chen, S., Wang, Q.-L., Xu, S., Liu, Y., Lili, Y.L., Wang, Y., & Zack, D.J. (2002). Functional analysis of cone-rod homeobox (CRX) mutations associated with retinal dystrophy. Human Molecular Genetics 11, 873–884.CrossRefGoogle Scholar
Chen, S. & Zack, D.J. (1996). Ret 4, a positive acting rhodopsin regulatory element identified using a bovine retina in vitro transcription system. Journal of Biological Chemistry 271, 28549–28557.CrossRefGoogle Scholar
Chen, S. & Zack, D.J. (2000). Cloning and characterization of retinal transcription factors, using target site-based methodology. Methods in Enzymology 316, 590–610.CrossRefGoogle Scholar
Cheng, H., Khanna, H., Oh, E.C., Hicks, D., Mitton, K.P., & Swaroop, A. (2004). Photoreceptor-specific nuclear receptor NR2E3 functions as a transcriptional activator in rod photoreceptors. Human Molecular Genetics 13, 1563–1575.CrossRefGoogle Scholar
Euskirchen, G., Royce, T.E., Bertone, P., Martone, R., Rinn, J.L., Nelson, F.K., Sayward, F., Luscombe, N.M., Miller, P., Gerstein, M., Weissman, S., & Snyder, M. (2004). CREB binds to multiple loci on human chromosome 22. Molecular and Cellular Biology 24, 3804–3814.CrossRefGoogle Scholar
Fei, Y., Matragoon, S., Smith, S.B., Overbeek, P.A., Chen, S., Zack, D.J., & Liou, G.I. (1999). Functional dissection of the promoter of the interphotoreceptor retinoid-binding protein gene: the cone-rod-homeobox element is essential for photoreceptor-specific expression in vivo. Journal of Biochemistry (Tokyo) 125, 1189–1199.CrossRefGoogle Scholar
Fong, S.L. & Fong, W.B. (1999). Elements regulating the transcription of human interstitial retinoid-binding protein (IRBP) gene in cultured retinoblastoma cells. Current Eye Research 18, 283–291.CrossRefGoogle Scholar
Freund, C.L., Gregory-Evans, C.Y., Furukawa, T., Papaioannou, M., Looser, J., Ploder, L., Bellingham, J., Ng, D., Herbrick, J.A., Duncan, A., Scherer, S.W., Tsui, L.C., Loutradis-Anagnostou, A., Jacobson, S.G., Cepko, C.L., Bhattacharya, S.S., & McInnes, R.R. (1997). Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor. Cell 91, 543–553.CrossRefGoogle Scholar
Freund, C.L., Wang, Q.L., Chen, S., Muskat, B.L., Wiles, C.D., Sheffield, V.C., Jacobson, S.G., McInnes, R.R., Zack, D.J., & Stone, E.M. (1998). De novo mutations in the CRX homeobox gene associated with Leber congenital amaurosis. Nature Genetics 18, 311–312.CrossRefGoogle Scholar
Furukawa, T., Morrow, E.M., & Cepko, C.L. (1997). Crx, a novel otx-like homeobox gene, shows photoreceptor-specific expression and regulates photoreceptor differentiation. Cell 91, 531–541.CrossRefGoogle Scholar
Furukawa, T., Morrow, E.M., Li, T., Davis, F.C., & Cepko, C.L. (1999). Retinopathy and attenuated circadian entrainment in Crx-deficient mice. Nature Genetics 23, 466–470.CrossRefGoogle Scholar
Ghosh, P.K., Baskaran, N., & van den Pol, A.N. (1997). Developmentally regulated gene expression of all eight metabotropic glutamate receptors in hypothalamic suprachiasmatic and arcuate nuclei–a PCR analysis. Brain Research Developmental Brain Research 102, 1–12.Google Scholar
Haider, N.B., Jacobson, S.G., Cideciyan, A.V., Swiderski, R., Streb, L.M., Searby, C., Beck, G., Hockey, R., Hanna, D.B., Gorman, S., Duhl, D., Carmi, R., Bennett, J., Weleber, R.G., Fishman, G.A., Wright, A.F., Stone, E.M., & Sheffield, V.C. (2000). Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate. Nature Genetics 24, 127–131.CrossRefGoogle Scholar
Haider, N.B., Naggert, J.K., & Nishina, P.M. (2001). Excess cone cell proliferation due to lack of a functional NR2E3 causes retinal dysplasia and degeneration in rd7/rd7 mice. Human Molecular Genetics 10, 1619–1626.CrossRefGoogle Scholar
Haruta, M., Kosaka, M., Kanegae, Y., Saito, I., Inoue, T., Kageyama, R., Nishida, A., Honda, Y., & Takahashi, M. (2001). Induction of photoreceptor-specific phenotypes in adult mammalian iris tissue. Nature Neuroscience 12, 12.CrossRefGoogle Scholar
Hug, B.A., Ahmed, N., Robbins, J.A., & Lazar, M.A. (2004). A chromatin immunoprecipitation screen reveals protein kinase Cbeta as a direct RUNX1 target gene. Journal of Biological Chemistry 279, 825–830.CrossRefGoogle Scholar
Impey, S., McCorkle, S.R., Cha-Molstad, H., Dwyer, J.M., Yochum, G.S., Boss, J.M., McWeeney, S., Dunn, J.J., Mandel, G., & Goodman, R.H. (2004). Defining the CREB regulon: A genome-wide analysis of transcription factor regulatory regions. Cell 119, 1041–1054.CrossRefGoogle Scholar
Irvine, R.A. & Hsieh, C.L. (2004). Q-PCR in combination with ChIP assays to detect changes in chromatin acetylation. Methods in Molecular Biology 287, 45–52.Google Scholar
Kirmizis, A., Bartley, S.M., Kuzmichev, A., Margueron, R., Reinberg, D., Green, R., & Farnham, P.J. (2004). Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27. Genes and Development 18, 1592–1605.CrossRefGoogle Scholar
Kirmizis, A. & Farnham, P.J. (2004). Genomic approaches that aid in the identification of transcription factor target genes. Experimental Biology and Medicine (Maywood) 229, 705–721.CrossRefGoogle Scholar
Kobayashi, M., Takezawa, S., Hara, K., Yu, R.T., Umesono, Y., Agata, K., Taniwaki, M., Yasuda, K., & Umesono, K. (1999). Identification of a photoreceptor cell-specific nuclear receptor. Proceedings of the National Academy of Sciences of the U.S.A. 96, 4814–4819.CrossRefGoogle Scholar
Kumar, R., Chen, S., Scheurer, D., Wang, Q.L., Duh, E., Sung, C.H., Rehemtulla, A., Swaroop, A., Adler, R., & Zack, D.J. (1996). The bZIP transcription factor Nrl stimulates rhodopsin promoter activity in primary retinal cell cultures. Journal of Biological Chemistry 271, 29612–29618.CrossRefGoogle Scholar
La Spada, A.R., Fu, Y.H., Sopher, B.L., Libby, R.T., Wang, X., Li, L.Y., Einum, D.D., Huang, J., Possin, D.E., Smith, A.C., Martinez, R.A., Koszdin, K.L., Treuting, P.M., Ware, C.B., Hurley, J.B., Ptacek, L.J., & Chen, S. (2001). Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone–rod dystrophy in a mouse model of SCA7. Neuron 31, 913–927.CrossRefGoogle Scholar
Liu, J.K., Bergman, Y., & Zaret, K.S. (1988). The mouse albumin promoter and a distal upstream site are simultaneously DNase I hypersensitive in liver chromatin and bind similar liver-abundant factors in vitro. Genes and Development 2, 528–541.CrossRefGoogle Scholar
Livesey, F.J., Furukawa, T., Steffen, M.A., Church, G.M., & Cepko, C.L. (2000). Microarray analysis of the transcriptional network controlled by the photoreceptor homeobox gene Crx. Current Biology 10, 301–310.CrossRefGoogle Scholar
Manuel, M., Rallu, M., Loones, M.T., Zimarino, V., Mezger, V., & Morange, M. (2002). Determination of the consensus binding sequence for the purified embryonic heat shock factor 2. European Journal of Biochemistry 269, 2527–2537.CrossRefGoogle Scholar
Mao, D.Y., Watson, J.D., Yan, P.S., Barsyte-Lovejoy, D., Khosravi, F., Wong, W.W., Farnham, P.J., Huang, T.H., & Penn, L.Z. (2003). Analysis of Myc bound loci identified by CpG island arrays shows that Max is essential for Myc-dependent repression. Current Biology 13, 882–886.CrossRefGoogle Scholar
Martinez-Morales, J.R., Dolez, V., Rodrigo, I., Zaccarini, R., Leconte, L., Bovolenta, P., & Saule, S. (2003). OTX2 activates the molecular network underlying retina pigment epithelium differentiation. Journal of Biological Chemistry 278, 21721–21731.CrossRefGoogle Scholar
Martone, R., Euskirchen, G., Bertone, P., Hartman, S., Royce, T.E., Luscombe, N.M., Rinn, J.L., Nelson, F.K., Miller, P., Gerstein, M., Weissman, S., & Snyder, M. (2003). Distribution of NF-kappaB-binding sites across human chromosome 22. Proceedings of the National Academy of Sciences of the U.S.A. 100, 12247–12252.CrossRefGoogle Scholar
Mears, A.J., Kondo, M., Swain, P.K., Takada, Y., Bush, R.A., Saunders, T.L., Sieving, P.A., & Swaroop, A. (2001). Nrl is required for rod photoreceptor development. Nature Genetics 29, 447–452.CrossRefGoogle Scholar
Milam, A.H., Rose, L., Cideciyan, A.V., Barakat, M.R., Tang, W.X., Gupta, N., Aleman, T.S., Wright, A.F., Stone, E.M., Sheffield, V.C., & Jacobson, S.G. (2002). The nuclear receptor NR2E3 plays a role in human retinal photoreceptor differentiation and degeneration. Proceedings of the National Academy of Sciences of the U.S.A. 99, 473–478.CrossRefGoogle Scholar
Mitton, K.P., Swain, P.K., Chen, S., Xu, S., Zack, D.J., & Swaroop, A. (2000). The leucine zipper of NRL interacts with the CRX homeodomain. A possible mechanism of transcriptional synergy in rhodopsin regulation. Journal of Biological Chemistry 275, 29794–29799.CrossRefGoogle Scholar
Ng, L., Hurley, J.B., Dierks, B., Srinivas, M., Salto, C., Vennstrom, B., Reh, T.A., & Forrest, D. (2001). A thyroid hormone receptor that is required for the development of green cone photoreceptors. Nature Genetics 27, 94–98.Google Scholar
Nguyen Ba-Charvet, K.T., von Boxberg, Y., & Godement, P. (1999). The mouse homeodomain protein OTX2 regulates NCAM promoter activity. Brain Research Molecular Brain Research 67, 292–295.CrossRefGoogle Scholar
Nie, Z., Chen, S., Kumar, R., & Zack, D.J. (1996). RER, an evolutionarily conserved sequence upstream of the rhodopsin gene, has enhancer activity. Journal of Biological Chemistry 271, 2667–2675.CrossRefGoogle Scholar
Nishida, A., Furukawa, A., Koike, C., Tano, Y., Aizawa, S., Matsuo, I., & Furukawa, T. (2003). Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development. Nature Neuroscience 6, 1255–1263.CrossRefGoogle Scholar
Odom, D.T., Zizlsperger, N., Gordon, D.B., Bell, G.W., Rinaldi, N.J., Murray, H.L., Volkert, T.L., Schreiber, J., Rolfe, P.A., Gifford, D.K., Fraenkel, E., Bell, G.I., & Young, R.A. (2004). Control of pancreas and liver gene expression by HNF transcription factors. Science 303, 1378–1381.CrossRefGoogle Scholar
Peng, G.H., Ahmad, O., Ahmad, F., Liu, J., & Chen, S. (2005). The photoreceptor-specific nuclear receptor Nr2e3 interacts with Crx and exerts opposing effects on the transcription of rod versus cone genes. Human Molecular Genetics 14, 747–764.CrossRefGoogle Scholar
Pittler, S.J., Zhang, Y., Chen, S., Mears, A.J., Zack, D.J., Ren, Z., Swain, P.K., Yao, S., Swaroop, A., & White, J.B. (2004). Functional analysis of the rod photoreceptor cGMP phosphodiesterase alpha-subunit gene promoter: Nrl and Crx are required for full transcriptional activity. Journal of Biological Chemistry 279, 19800–19807.CrossRefGoogle Scholar
Potratz, J.C., Mlody, B., Berdel, W.E., Serve, H., & Muller-Tidow, C. (2005). In vivo analyses of UV-irradiation-induced p53 promoter binding using a novel quantitative real-time PCR assay. International Journal of Oncology 26, 493–498.Google Scholar
Rehemtulla, A., Warwar, R., Kumar, R., Ji, X., Zack, D.J., & Swaroop, A. (1996). The basic motif-leucine zipper transcription factor Nrl can positively regulate rhodopsin gene expression. Proceedings of the National Academy of Sciences of the U.S.A. 93, 191–195.CrossRefGoogle Scholar
Ren, B., Cam, H., Takahashi, Y., Volkert, T., Terragni, J., Young, R.A., & Dynlacht, B.D. (2002). E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints. Genes and Development 16, 245–256.CrossRefGoogle Scholar
Rivolta, C., Berson, E.L., & Dryja, T.P. (2001). Dominant Leber congenital amaurosis, cone-rod degeneration, and retinitis pigmentosa caused by mutant versions of the transcription factor CRX. Human Mutation 18, 488–498.CrossRefGoogle Scholar
Roulet, E., Busso, S., Camargo, A.A., Simpson, A.J., Mermod, N., & Bucher, P. (2002). High-throughput SELEX SAGE method for quantitative modeling of transcription-factor binding sites. Nature Biotechnology 20, 831–835.CrossRefGoogle Scholar
Schlamp, C.L., Johnson, E.C., Li, Y., Morrison, J.C., & Nickells, R.W. (2001). Changes in Thy1 gene expression associated with damaged retinal ganglion cells. Molecular Vision 7, 192–201.Google Scholar
Simeone, A., Acampora, D., Gulisano, M., Stornaiuolo, A., & Boncinelli, E. (1992). Nested expression domains of four homeobox genes in developing rostral brain. Nature 358, 687–690.CrossRefGoogle Scholar
Sohocki, M.M., Daiger, S.P., Bowne, S.J., Rodriquez, J.A., Northrup, H., Heckenlively, J.R., Birch, D.G., Mintz-Hittner, H., Ruiz, R.S., Lewis, R.A., Saperstein, D.A., & Sullivan, L.S. (2001). Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies. Human Mutation 17, 42–51.3.0.CO;2-K>CrossRefGoogle Scholar
Soucy, E., Wang, Y., Nirenberg, S., Nathans, J., & Meister, M. (1998). A novel signaling pathway from rod photoreceptors to ganglion cells in mammalian retina. Neuron 21, 481–493.CrossRefGoogle Scholar
Swain, P.K., Chen, S., Wang, Q.L., Affatigato, L.M., Coats, C.L., Brady, K.D., Fishman, G.A., Jacobson, S.G., Swaroop, A., Stone, E., Sieving, P.A., & Zack, D.J. (1997). Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration. Neuron 19, 1329–1336.CrossRefGoogle Scholar
Swaroop, A., Wang, Q.L., Wu, W., Cook, J., Coats, C., Xu, S., Chen, S., Zack, D.J., & Sieving, P.A. (1999). Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: Direct evidence for the involvement of CRX in the development of photoreceptor function. Human Molecular Genetics 8, 299–305.CrossRefGoogle Scholar
Swaroop, A., Xu, J.Z., Pawar, H., Jackson, A., Skolnick, C., & Agarwal, N. (1992). A conserved retina-specific gene encodes a basic motif/leucine zipper domain. Proceedings of the National Academy of Sciences of the U.S.A. 89, 266–270.CrossRefGoogle Scholar
Ueda, Y., Iwakabe, H., Masu, M., Suzuki, M., & Nakanishi, S. (1997). The mGluR6 5′ upstream transgene sequence directs a cell-specific and developmentally regulated expression in retinal rod and ON-type cone bipolar cells. Journal of Neuroscience 17, 3014–3023.Google Scholar
Velculescu, V.E., Zhang, L., Vogelstein, B., & Kinzler, K.W. (1995). Serial analysis of gene expression. Science 270, 484–487.CrossRefGoogle Scholar
Wang, X., Xu, S., Rivolta, C., Li, L.Y., Peng, G.H., Swain, P.K., Sung, C.H., Swaroop, A., Berson, E.L., Dryja, T.P., & Chen, S. (2002). Barrier to autointegration factor interacts with the cone-rod homeobox and represses its transactivation function. Journal of Biological Chemistry 277, 43288–43300.CrossRefGoogle Scholar
Wang, Y., Macke, J.P., Merbs, S.L., Zack, D.J., Klaunberg, B., Bennett, J., Gearhart, J., & Nathans, J. (1992). A locus control region adjacent to the human red and green visual pigment genes. Neuron 9, 429–440.CrossRefGoogle Scholar
Weinmann, A.S., Bartley, S.M., Zhang, T., Zhang, M.Q., & Farnham, P.J. (2001). Use of chromatin immunoprecipitation to clone novel E2F target promoters. Molecular and Cellular Biology 21, 6820–6832.CrossRefGoogle Scholar
Weinmann, A.S., Yan, P.S., Oberley, M.J., Huang, T.H., & Farnham, P.J. (2002). Isolating human transcription factor targets by coupling chromatin immunoprecipitation and CpG island microarray analysis. Genes and Development 16, 235–244.CrossRefGoogle Scholar
Wells, J. & Farnham, P.J. (2002). Characterizing transcription factor binding sites using formaldehyde crosslinking and immunoprecipitation. Methods 26, 48–56.Google Scholar
Wells, J., Graveel, C.R., Bartley, S.M., Madore, S.J., & Farnham, P.J. (2002). The identification of E2F1-specific target genes. Proceedings of the National Academy of Sciences of the U.S.A. 99, 3890–3895.CrossRefGoogle Scholar
Wells, J., Yan, P.S., Cechvala, M., Huang, T., & Farnham, P.J. (2003). Identification of novel pRb binding sites using CpG microarrays suggests that E2F recruits pRb to specific genomic sites during S phase. Oncogene 22, 1445–1460.CrossRefGoogle Scholar
Yan, R.T. & Wang, S.Z. (2004). Requirement of neuroD for photoreceptor formation in the chick retina. Investigative Ophthalmology and Visual Science 45, 48–58.CrossRefGoogle Scholar
Yoshida, S., Mears, A.J., Friedman, J.S., Carter, T., He, S., Oh, E., Jing, Y., Farjo, R., Fleury, G., Barlow, C., Hero, A.O., & Swaroop, A. (2004). Expression profiling of the developing and mature Nrl−/− mouse retina: Identification of retinal disease candidates and transcriptional regulatory targets of Nrl. Human Molecular Genetics 13, 1487–1503.CrossRefGoogle Scholar
Yu, J., He, S., Friedman, J.S., Akimoto, M., Ghosh, D., Mears, A.J., Hicks, D., & Swaroop, A. (2004). Altered expression of genes of the Bmp/Smad and Wnt/calcium signaling pathways in the cone-only Nrl−/− mouse retina, revealed by gene profiling using custom cDNA microarrays. Journal of Biological Chemistry 279, 42211–42220.CrossRefGoogle Scholar
Zareparsi, S., Hero, A., Zack, D.J., Williams, R.W., & Swaroop, A. (2004). Seeing the unseen: Microarray-based gene expression profiling in vision. Investigative Ophthalmology and Visual Science 45, 2457–2462.CrossRefGoogle Scholar
Zhang, J., Gray, J., Wu, L., Leone, G., Rowan, S., Cepko, C.L., Zhu, X., Craft, C.M., & Dyer, M.A. (2004). Rb regulates proliferation and rod photoreceptor development in the mouse retina. Nature Genetics 36, 351–360.CrossRefGoogle Scholar