Di‐ and trimethylation of lysine 27 on histone 3 (H3K27me2/3) is a critical gene repression mechanism. We previously showed that down‐regulation of the H3K27 demethylase, Jumonji domain‐containing protein 3 (JMJD3), resulted in a reduced number of protein kinase C (PKC)α‐positive rod ON‐bipolar cells. In this work, we focused on the role of another H3K27 demethylase, ubiquitously transcribed tetratricopeptide repeat X chromosome (UTX), in retinal development. UTX was expressed in the retinal progenitor cells of the embryonic mouse retina and was observed in the inner nuclear layer during late retinal development and in the mature retina. The short hairpin RNA‐mediated knockdown of Utx in a mouse retinal explant led to a reduced number of PKCα‐positive rod ON‐bipolar cells. However, other retinal subtypes were unaffected by this knockdown. Using a retina‐specific knockout of Utx in mice, the in vivo effects of UTX down‐regulation were examined. Again, the number of PKCα‐positive rod ON‐bipolar cells was reduced, and no other apparent phenotypes, including retinal progenitor proliferation, apoptosis or differentiation, were observed. Finally, we examined retina‐specific Utx and Jmjd3 double‐knockout mice and found that although the number of rod ON‐bipolar cells was reduced, no additional effects from the loss of Utx and Jmjd3 were observed. Taken together, our data show that UTX contributes to retinal differentiation in a lineage‐specific manner.

中文翻译：

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H3K27me3脱甲基酶UTX调节小鼠视网膜中双极细胞子集的分化。

组蛋白3（H3K27me2 / 3）上赖氨酸27的二甲基和三甲基化是关键的基因抑制机制。我们先前发现，H3K27脱甲基酶（包含Jumonji域的蛋白3（JMJD3））的下调导致蛋白激酶C（PKC）α阳性杆状双极细胞数量减少。在这项工作中，我们专注于另一种H3K27脱甲基酶，在视网膜发育中无处不在地转录四三肽重复X染色体（UTX）。UTX在胚胎小鼠视网膜的视网膜祖细胞中表达，并在视网膜后期发育和成熟视网膜中的内核层中观察到。短发夹RNA介导的Utx敲低小鼠视网膜外植体中的PKCα阳性杆上双极细胞数量减少。但是，其他视网膜亚型不受此击倒的影响。使用小鼠中Utx的视网膜特异性敲除，检查了UTX下调的体内作用。同样，PKCα阳性杆上双极细胞的数量减少了，没有观察到其他明显的表型，包括视网膜祖细胞的增殖，凋亡或分化。最后，我们检查了视网膜特异性Utx和Jmjd3双敲除小鼠，发现尽管杆状双极杆细胞数量减少了，但Utx和Jmjd3的丢失没有其他影响被观察。综上所述，我们的数据表明，UTX以谱系特异性方式促进视网膜分化。