Unique Functions of Repetitive Transcriptomes

Schumann, Gerald G.; Gogvadze, Elena; Osanai-Futahashi, Mizuko; Kuroki, Azusa; Münk, Carsten; Fujiwara, Haruko; Ivics, Zoltán; Buzdin, Anton

doi:10.1016/b978-0-12-381047-2.00003-7

Cited by 53 publications

(51 citation statements)

References 419 publications

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“…Genomic copies of HERVs are of particular interest because in addition to functional viral genes, they have multitude of regulatory DNA regions serving as promoters [1][2][3], enhancers [4,5], polyadenylation signals [6,7], insulators [8,9] and binding sites for various nuclear proteins [2,[10][11][12][13]. Many families of HERVs exhibit high transcriptional activity in human tissues [1,[14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Molecular functions of human endogenous retroviruses in health and disease

Suntsova

Garazha

Ivanova

et al. 2015

Cell. Mol. Life Sci.

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Human endogenous retroviruses (HERVs) and related genetic elements form 504 distinct families and occupy ~8% of human genome. Recent success of high-throughput experimental technologies facilitated understanding functional impact of HERVs for molecular machinery of human cells. HERVs encode active retroviral proteins, which may exert important physiological functions in the body, but also may be involved in the progression of cancer and numerous human autoimmune, neurological and infectious diseases. The spectrum of related malignancies includes, but not limits to, multiple sclerosis, psoriasis, lupus, schizophrenia, multiple cancer types and HIV. In addition, HERVs regulate expression of the neighboring host genes and modify genomic regulatory landscape, e.g., by providing regulatory modules like transcription factor binding sites (TFBS). Indeed, recent bioinformatic profiling identified ~110,000 regulatory active HERV elements, which formed at least ~320,000 human TFBS. These and other peculiarities of HERVs might have played an important role in human evolution and speciation. In this paper, we focus on the current progress in understanding of normal and pathological molecular niches of HERVs, on their implications in human evolution, normal physiology and disease. We also review the available databases dealing with various aspects of HERV genetics.

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Section: Introductionmentioning

confidence: 99%

Molecular functions of human endogenous retroviruses in health and disease

Suntsova

Garazha

Ivanova

et al. 2015

Cell. Mol. Life Sci.

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“…Given, this finding and the significant metabolic expense of such an event, the addition of the third methyl group being, energetically, a very expensive epigenetic modification, we hypothesized that H3K9me3 suppresses the stress-induced activation of repetitive and transposable elements. These elements comprise a much larger proportion of the mammalian genome (∼50%) than do genes themselves (less than 5%) (14) and contribute to genomic instability (15), a significant problem for postmitotic neurons that must remain phenotypically stable for years or even decades. Here we show that stress-induced increases in H3K9me3 in the hippocampus are strongly targeted to retrotransposable elements and rapidly silence their expression.…”

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confidence: 99%

Acute stress and hippocampal histone H3 lysine 9 trimethylation, a retrotransposon silencing response

Hunter

Murakami

Dewell

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

163

117

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The hippocampus is a highly plastic brain region particularly susceptible to the effects of environmental stress; it also shows dynamic changes in epigenetic marks in response to stress and learning. We have previously shown that, in the rat, acute (30 min) restraint stress induces a substantial, regionally specific, increase in hippocampal levels of the repressive histone H3 lysine 9 trimethylation (H3K9me3). Because of the large magnitude of this effect and the fact that stress can induce the expression of endogenous retroviruses and transposable elements in many systems, we hypothesized that the H3K9me3 response was targeted to these elements as a means of containing potential genomic instability. We used ChIP coupled with next generation sequencing (ChIP-Seq) to determine the genomic localization of the H3K9me3 response. Although there was a general increase in this response across the genome, our results validated this hypothesis by demonstrating that stress increases H3K9me3 enrichment at transposable element loci and, using RT-PCR, we demonstrate that this effect represses expression of intracisternal-A particle endogenous retrovirus elements and B2 short interspersed elements, but it does not appear to have a repressive effect on long interspersed element RNA. In addition, we present data showing that the histone H3K9-specific methyltransferases Suv39h2 is up-regulated by acute stress in the hippocampus, and that this may explain the hippocampal specificity we observe. These results are a unique demonstration of the regulatory effect of environmental stress, via an epigenetic mark, on the vast genomic terra incognita represented by transposable elements.heterochromatin | ncRNA | posttraumatic stress disorder | transposon

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“…From McClintock's earliest experiments, it was clear that TEs can alter regulation of gene expression, and there is a long history of observations detailing the ways in which they can do so (King, 1985;Britten, 1996;Kidwell and Lisch, 2001;Dooner and Weil, 2007;Schumann et al, 2010). The details of McClintock's observations have been described extensively elsewhere (Fedoroff, 1989a;Fedoroff, 1989b), but the broad implications of those observations deserve to be emphasized here.…”

Section: New Regulatory Functionsmentioning

confidence: 98%

Transposons in Plant Gene Regulation

Lisch

2013

Plant Transposons and Genome Dynamics in Evolution

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Unique Functions of Repetitive Transcriptomes

Cited by 53 publications

References 419 publications

Molecular functions of human endogenous retroviruses in health and disease

Molecular functions of human endogenous retroviruses in health and disease

Acute stress and hippocampal histone H3 lysine 9 trimethylation, a retrotransposon silencing response

Transposons in Plant Gene Regulation

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