Analysis of epigenetic regulation of cone opsin expression by COUP-TF nuclear receptors

• Project/Area Number: 21770136
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: The University of Tokyo
• Principal Investigator: SATOH Shinya The University of Tokyo, 医科学研究所, 特任助教 (80333558)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 網膜 / 核内受容体 / オプシン

Research Abstract

Previously we demonstrated that COUP-TF nuclear receptors contribute to the establishment of dorso-ventral expression pattern of cone opsins in mouse retina. In this study I'd like to clarify the mechanism of this regulation by focusing on epigenetic mechanism. I analyzed DNA methylation status of dorsal- and ventral-region of mouse retina, or DNA methylation and histone modification status in retinoblastoma cell line in which endogenous COUP-TFs were knocked down by shRNA. However, significant correlation between COUP-TFs expression and these epigenetic status has not been seen yet. On the other hand, I identified TRbeta2 regulating genomic region in human red opsin gene and found that COUP-TFs show the different effect on TRbeta2-mediated activation in this genomic region between human and mouse genome. Furthermore, I found that Brg1, a chromatin remodeling factor, activates blue opsin gene expression and COUP-TFs suppress this Brg1-mediated activation. These results suggest that COUP-TFs regulate cone opsin expression in retina through interaction of these factors, which establishes each animal specific cone opsin expression pattern.

Research Products

• [Journal Article] COUP-TFI and -TFII nuclear receptors are expressed in amacrine cells and play roles in regulating the differentiation of retinal progenitor cells. (2010)
  • Author(s): Inoue M, Iida A, Satoh S, Kodama T, Watanabe S.
  • Journal Title: Experimental Eye Research Vol.90, No.1 Pages: 49-56
  • Peer Reviewed
• [Journal Article] The spatial patterning of mouse cone opsin expression is regulated by bone morphogenetic protein signaling through downstream effector COUP-TF nuclear receptors. (2009)
  • Author(s): Satoh S, Tang K, Iida A, Inoue M, Kodama T, Tsai SY, Tsai MJ, Furuta Y, Watanabe S.
  • Journal Title: Jouranl of Neuroscience Vol.29, No.40 Pages: 12401-12411
  • Peer Reviewed
• [Journal Article] The spatial patterning of mouse cone opsin expression is regulated byBMP signaling through downstream effector COUP-TF nuclear receptors (2009)
  • Author(s): Satoh, S., et al.
  • Journal Title: J.Neurosci. 29 Pages: 12401-12411
  • Peer Reviewed
• [Presentation] The spatial patterning of mouse cone opsin expression is regulated by BMP signaling through downstream effector COUP-TF nuclear receptors. (2009)
  • Author(s): 佐藤伸哉
  • Place of Presentation: 沖縄県恩納村OISTシーサイドハウス
• [Presentation] The spatial patterning of mouse cone opsin expression is regulated by BMP signaling through downstream effector COUP-TF nuclear receptors (2009)
  • Author(s): 佐藤伸哉
  • Organizer: GIST International Workshop The Retina : Neura Stem Cells and Photoreceptor Degeneration
  • Place of Presentation: 沖縄県恩納村OISTシーサイドハウス
• [Remarks] ホームページ
  • URL: http://www.ims.u-tokyo.ac.jp/moldev/