Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
Department of Ophthalmology, University of California Irvine, Irvine, CA 92697.
Proc Natl Acad Sci U S A. 2024 Nov 19;121(47):e2402121121. doi: 10.1073/pnas.2402121121. Epub 2024 Nov 12.
The role of transcription factors in photoreceptor gene regulation is fairly well understood, but knowledge of the cell-type-specific function of transcriptional cofactors remains incomplete. Here, we show that the transcriptional corepressor promotes rod differentiation and represses short-wavelength cone genes in long-wavelength cones in zebrafish. In retinas, red cones are transformed into hybrid red/ultraviolet (UV) cones, green cones are absent, the number of blue cones is approximately doubled, and the number of rods is greatly reduced. We also find that mouse represses S-opsin expression in dorsal M-cones-analogous to its role in repressing UV cone genes in zebrafish red cones. Thus, plays a key role in ensuring appropriate patterns of gene expression in rods and cone subtypes of both zebrafish and mice.
转录因子在光感受器基因调控中的作用已经相当清楚,但转录共激活因子的细胞类型特异性功能的知识仍然不完整。在这里,我们表明,转录核心抑制因子 在斑马鱼中促进视杆分化并抑制长波视锥细胞中的短波视锥基因。在 视网膜中,红色视锥细胞转化为混合的红色/紫外线(UV)视锥细胞,绿色视锥细胞缺失,蓝色视锥细胞的数量大约增加了一倍,视杆细胞的数量大大减少。我们还发现,小鼠 抑制背侧 M-视锥细胞中的 S-视蛋白表达-类似于其在斑马鱼红色视锥细胞中抑制 UV 视锥基因的作用。因此, 在确保斑马鱼和小鼠的视杆细胞和视锥细胞亚型中适当的基因表达模式方面发挥着关键作用。