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Evolutionary dynamics of roX lncRNA function and genomic occupancy

Jeffrey J. Quinn, Qiangfeng C. Zhang, Plamen Georgiev, Ibrahim A. Ilik, Asifa Akhtar, Howard Y. Chang
doi: https://doi.org/10.1101/026013
Jeffrey J. Quinn
1Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, California, USA
2Department of Bioengineering, Stanford University School of Medicine and School of Engineering, Stanford, California, USA
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Qiangfeng C. Zhang
1Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, California, USA
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Plamen Georgiev
3Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, Freiburg im Breisgau, Germany
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Ibrahim A. Ilik
3Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, Freiburg im Breisgau, Germany
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Asifa Akhtar
3Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, Freiburg im Breisgau, Germany
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Howard Y. Chang
1Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, California, USA
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Abstract

Many long noncoding RNAs (lncRNAs) can regulate chromatin states, but the evolutionary origin and dynamics driving lncRNA–genome interactions are unclear. We developed an integrative strategy that identifies lncRNA orthologs in different species despite limited sequence similarity that is applicable to fly and mammalian lncRNAs. Analysis of the roX lncRNAs, which are essential for dosage compensation of the single X-chromosome in Drosophila males, revealed 47 new roX orthologs in diverse Drosophilid species across ∼40 million years of evolution. Genetic rescue by roX orthologs and engineered synthetic lncRNAs showed that evolutionary maintenance of focal structural repeats mediates roX function. Genomic occupancy maps of roX RNAs in four species revealed rapid turnover of individual binding sites but conservation within nearby chromosomal neighborhoods. Many new roX binding sites evolved from DNA encoding a pre-existing RNA splicing signal, effectively linking dosage compensation to transcribed genes. Thus, evolutionary analysis illuminates the principles for the birth and death of lncRNAs and their genomic targets.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 04, 2015.
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Evolutionary dynamics of roX lncRNA function and genomic occupancy
Jeffrey J. Quinn, Qiangfeng C. Zhang, Plamen Georgiev, Ibrahim A. Ilik, Asifa Akhtar, Howard Y. Chang
bioRxiv 026013; doi: https://doi.org/10.1101/026013
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Evolutionary dynamics of roX lncRNA function and genomic occupancy
Jeffrey J. Quinn, Qiangfeng C. Zhang, Plamen Georgiev, Ibrahim A. Ilik, Asifa Akhtar, Howard Y. Chang
bioRxiv 026013; doi: https://doi.org/10.1101/026013

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