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首页> 外文期刊>Cell cycle >Replication-dependent histone genes are actively transcribed in differentiating and aging retinal neurons
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Replication-dependent histone genes are actively transcribed in differentiating and aging retinal neurons

机译：复制依赖性组蛋白基因在分化和衰老的视网膜神经元中活跃转录。

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In the mammalian genome, each histone family contains multiple replication-dependent paralogs, which are found in clusters where their transcription is thought to be coupled to the cell cycle. Here, we wanted to interrogate the transcriptional regulation of these paralogs during retinal development and aging. We employed deep sequencing, quantitative PCR, in situ hybridization (ISH), and microarray analysis, which revealed that replication-dependent histone genes were not only transcribed in progenitor cells but also in differentiating neurons. Specifically, by ISH analysis we found that different histone genes were actively transcribed in a subset of neurons between postnatal day 7 and 14. Interestingly, within a histone family, not all paralogs were transcribed at the same level during retinal development. For example, expression of Hist1h1b was higher embryonically, while that of Hist1h1c was higher postnatally. Finally, expression of replication-dependent histone genes was also observed in the aging retina. Moreover, transcription of replication-dependent histones was independent of rapamycin-mediated mTOR pathway inactivation. Overall, our data suggest the existence of variant nucleosomes produced by the differential expression of the replication-dependent histone genes across retinal development. Also, the expression of a subset of replication-dependent histone isotypes in senescent neurons warrants re-examining these genes as "replication-dependent. " Thus, our findings underscore the importance of understanding the transcriptional regulation of replication-dependent histone genes in the maintenance and functioning of neurons.
机译：在哺乳动物基因组中，每个组蛋白家族均包含多个复制依赖性旁系同源物，这些旁系同源物存在于簇中，在簇中它们的转录被认为与细胞周期相关。在这里，我们想询问视网膜发育和衰老过程中这些旁系同源物的转录调控。我们采用了深度测序，定量PCR，原位杂交（ISH）和微阵列分析，结果表明复制依赖性组蛋白基因不仅在祖细胞中转录，而且在分化神经元中转录。具体而言，通过ISH分析，我们发现在出生后第7天到第14天之间，不同的组蛋白基因在神经元的一个子集中活跃转录。有趣的是，在组蛋白家族中，并非所有旁系同源物在视网膜发育过程中都以相同的水平转录。例如，Hist1h1b的表达在胚胎中较高，而Hist1h1c的表达在出生后较高。最后，在衰老的视网膜中还观察到复制依赖性组蛋白基因的表达。此外，复制依赖性组蛋白的转录独立于雷帕霉素介导的mTOR途径失活。总的来说，我们的数据表明存在通过视网膜发育过程中复制依赖性组蛋白基因的差异表达而产生的变异核小体。另外，衰老神经元中复制依赖的组蛋白同种型的子集的表达保证将这些基因重新检查为“复制依赖”。因此，我们的发现强调了理解维持过程中复制依赖的组蛋白基因的转录调控的重要性。和神经元的功能。

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