依赖Pias3的SUMO化修饰指导视杆光感受器的发育。
Pias3-dependent SUMOylation directs rod photoreceptor development.
作者信息
Onishi Akishi, Peng Guang-Hua, Hsu Chengda, Alexis Uel, Chen Shiming, Blackshaw Seth
机构信息
Department of Neuroscience, Johns Hopkins University School of Medicine, BRB 329, 733 North Broadway Avenue, Baltimore, MD 21287, USA.
出版信息
Neuron. 2009 Jan 29;61(2):234-46. doi: 10.1016/j.neuron.2008.12.006.
Specification of retinal rod photoreceptors is determined by several different transcription factors that activate expression of rod-specific genes and repress expression of cone photoreceptor-specific genes. The mechanism by which this dual regulation occurs is unclear. We have found that Pias3, a transcriptional coregulator and E3 SUMO ligase that is selectively expressed in developing photoreceptors, promotes the differentiation of rod photoreceptors while preventing rods from adopting cone photoreceptor-like characteristics. Pias3 binds the photoreceptor-specific transcription factors Crx and Nr2e3 and is specifically targeted to the promoters of photoreceptor-specific genes. Pias3 SUMOylates Nr2e3, converting it into a potent repressor of cone-specific gene expression. Rod- and cone-specific promoters are bound by hyperSUMOylated proteins in rod photoreceptors, and blocking SUMOylation in photoreceptors results in cells with morphological and molecular features of cones and an absence of rod-specific markers. Our data thus identify Pias3-mediated SUMOylation of photoreceptor-specific transcription factors as a key mechanism of rod specification.
视网膜视杆光感受器的特化由几种不同的转录因子决定，这些转录因子激活视杆特异性基因的表达并抑制视锥光感受器特异性基因的表达。这种双重调节发生的机制尚不清楚。我们发现，Pias3是一种转录共调节因子和E3 SUMO连接酶，在发育中的光感受器中选择性表达，它促进视杆光感受器的分化，同时防止视杆细胞具有类似视锥光感受器的特征。Pias3与光感受器特异性转录因子Crx和Nr2e3结合，并特异性靶向光感受器特异性基因的启动子。Pias3使Nr2e3发生SUMO化，将其转化为视锥特异性基因表达的有效抑制因子。视杆和视锥特异性启动子在视杆光感受器中与高度SUMO化的蛋白质结合，并且在光感受器中阻断SUMO化会导致细胞具有视锥细胞的形态和分子特征，且缺乏视杆特异性标记物。因此，我们的数据确定了Pias3介导的光感受器特异性转录因子的SUMO化是视杆细胞特化的关键机制。
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