Replication-dependent histone genes are actively transcribed in differentiating and aging retinal neurons
| Autor: | Marybeth Baumgartner, Claudio Punzo, Ion I. Mandoiu, Aditya Venkatesh, Sahar Al Seesi, Rahul N. Kanadia, Ashley M Kilcollins, Sean Congdon, Abdul Rouf Banday, Christopher Lemoine, Devi Krishna Priya Karunakaran |
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| Rok vydání: | 2014 |
| Předmět: |
DNA Replication
Transcription Genetic Neurogenesis SAP30 Histones Mice Histone H1 Report Cyclin E Histone methylation Histone H2A Transcriptional regulation Animals Protein Isoforms Cyclin D1 RNA Messenger Molecular Biology Cellular Senescence Genetics biology HDAC11 Stem Cells TOR Serine-Threonine Kinases Cell Biology HDAC4 Histone biology.protein Retinal Neurons Developmental Biology |
| Zdroj: | Cell Cycle. 13:2526-2541 |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.4161/15384101.2015.941757 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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