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      Potential Role of Phase Separation of Repetitive DNA in Chromosomal Organization

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      Genes
      MDPI
      repetitive DNA, ‘junk’ DNA, repeat assembly, chromosome, chromatin, phase separation, CORE theory, membrane-less organelle

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          Abstract

          The basic principles of chromosomal organization in eukaryotic cells remain elusive. Current mainstream research efforts largely concentrate on searching for critical packaging proteins involved in organizing chromosomes. I have taken a different perspective, by considering the role of genomic information in chromatins. In particular, I put forward the concept that repetitive DNA elements are key chromosomal packaging modules, and their intrinsic property of homology-based interaction can drive chromatin folding. Many repetitive DNA families have high copy numbers and clustered distribution patterns in the linear genomes. These features may facilitate the interactions among members in the same repeat families. In this paper, the potential liquid–liquid phase transition of repetitive DNAs that is induced by their extensive interaction in chromosomes will be considered. I propose that the interaction among repetitive DNAs may lead to phase separation of interacting repetitive DNAs from bulk chromatins. Phase separation of repetitive DNA may provide a physical mechanism that drives rapid massive changes of chromosomal conformation.

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          Most cited references20

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          Mechanisms and Consequences of Macromolecular Phase Separation.

          Over a century ago, colloidal phase separation of matter into non-membranous bodies was recognized as a fundamental organizing principal of cell "protoplasm." Recent insights into the molecular properties of such phase-separated bodies present challenges to our understanding of cellular protein interaction networks, as well as opportunities for interpreting and understanding of native and pathological genetic and molecular interactions. Here, we briefly review examples of and discuss physical principles of phase-separated cellular bodies and then reflect on how knowledge of these principles may direct future research on their functions.
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            Repetitive sequences in complex genomes: structure and evolution.

            Eukaryotic genomes contain vast amounts of repetitive DNA derived from transposable elements (TEs). Large-scale sequencing of these genomes has produced an unprecedented wealth of information about the origin, diversity, and genomic impact of what was once thought to be "junk DNA." This has also led to the identification of two new classes of DNA transposons, Helitrons and Polintons, as well as several new superfamilies and thousands of new families. TEs are evolutionary precursors of many genes, including RAG1, which plays a role in the vertebrate immune system. They are also the driving force in the evolution of epigenetic regulation and have a long-term impact on genomic stability and evolution. Remnants of TEs appear to be overrepresented in transcription regulatory modules and other regions conserved among distantly related species, which may have implications for our understanding of their impact on speciation.
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              Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts.

              The abundance of Alu RNA is transiently increased by heat shock in human cell lines. This effect is specific to Alu repeats among Pol III transcribed genes, since the abundance of 7SL, 7SK, 5S and U6 RNAs is essentially unaffected by heat shock. The rapid induction of Alu expression precedes the heat shock induction of mRNAs for the ubiquitin and HSP 70 heat shock genes. Heat shock mimetics also transiently induce Alu expression indicating that increased Alu expression is a general cell-stress response. Cycloheximide treatment rapidly and transiently increases the abundance of Alu RNA. Again, compared with other genes transcribed by Pol III, this increase is specific to Alu. However, as distinguished from the cell stress response, cycloheximide does not induce expression of HSP 70 and ubiquitin mRNAs. Puromycin also increases Alu expression, suggesting that this response is generally caused by translational inhibition. The response of mammalian SINEs to cell stress and translational inhibition is not limited to SINEs which are Alu homologues. Heat shock and cycloheximide each transiently induce Pol III directed expression of B1 and B2 RNAs in mouse cells and C-element RNA in rabbit cells. Together, these three species exemplify the known SINE composition of placental mammals, suggesting that mammalian SINEs are similarly regulated and may serve a common function.
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                Author and article information

                Journal
                Genes (Basel)
                Genes (Basel)
                genes
                Genes
                MDPI
                2073-4425
                18 October 2017
                October 2017
                : 8
                : 10
                : 279
                Affiliations
                Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA; shtang@ 123456utmb.edu ; Tel.: +1-409-772-1190
                Author information
                https://orcid.org/0000-0002-6076-5481
                Article
                genes-08-00279
                10.3390/genes8100279
                5664129
                29057826
                6436803a-46df-434b-aa41-ea15cb1991c3
                © 2017 by the author.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 23 August 2017
                : 13 October 2017
                Categories
                Opinion

                repetitive dna,‘junk’ dna,repeat assembly,chromosome,chromatin,phase separation,core theory,membrane-less organelle

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