Who Needs This Junk, or Genomic Dark Matter

Podgornaya, O. I.; Ostromyshenskii, D. I.; Enukashvily, N. I.

doi:10.1134/s0006297918040156

Cited by 31 publications

(24 citation statements)

References 120 publications

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“…The complex nature of the alphoid repeat sequences precludes precise mapping of IS in centromeres, and, for this reason, they are not annotated in either the hg 19 or hg38 genome database and were not detected using our standard pipeline to identify and locate IS, even though the centromeres comprise approximately 7% of the genome [41]. [See, for an example, the large gene-free area around 40 Mb of chromosome 16 (Fig 3)].…”

Section: Integration In Centromeric Repeatsmentioning

confidence: 99%

Integration in oncogenes plays only a minor role in determining the in vivo distribution of HIV integration sites before or during suppressive antiretroviral therapy

et al. 2021

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Section: Integration In Centromeric Repeatsmentioning

confidence: 99%

Integration in oncogenes plays only a minor role in determining the in vivo distribution of HIV integration sites before or during suppressive antiretroviral therapy

et al. 2021

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“…The complex nature of the alphoid repeat sequences precludes precise mappting of IS in centromeres, and, for this reason, they are not annotated in the hg 19 (or hg38) genome database and were not detected using our the standard pipeline to identify and locate IS, even though the cetromeres comprise approximately 7% of the genome [40]. [See, for an example, the large gene-free area around 40 Mb of chromosome 16 (Figure 3)].…”

Section: Resultsmentioning

confidence: 99%

“…As expected, when all 5983 genes with IS in both the on-ART and the PBMC datasets were analyzed and ranked by the combined p value for the relative number of IS and for orientation bias, the three top ranking genes were MKL2, STAT5B, and BACH2. Three more genes were identified using the new on-ART dataset: MKL1 (also known as MRFTA), a paralogue of MKL2 [39]. All six genes have been linked directly to cell growth or survival (see Discussion).…”

Section: Cclustered Is In Specific Genesmentioning

confidence: 99%

Integration in or Near Oncogenes Plays Only a Minor Role in Determining the in Vivo Distribution of HIV Integration Sites Before or During Suppressive Antiretroviral Therapy

Coffin

Bale²,

Wells

et al. 2020

Preprint

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HIV persists during antiretroviral therapy (ART) as integrated proviruses in cells descended from a small fraction of the CD4+ T cells infected prior to the initiation of ART. To better understand what controls HIV persistence and the distribution of integration sites (IS), we compared about 16,000 and 54,000 IS from individuals pre-ART and on ART, respectively, with approximately 385,000 IS from PBMC infected in vitro. The distribution of IS in vivo is quite similar to the distribution in PBMC, modified by selection against proviruses in expressed genes, by selection for proviruses integrated into one of 6 specific genes, and by clonal expansion. The clones in which a provirus integrated in an oncogene contributed to the survival of the clone comprise only a small fraction of the clones that persist in HIV-infected individuals on ART. Mechanisms that do not involve the provirus, or its location in the host genome, are more important in determining which clones expand and persist.Author SummaryIn HIV-infected individuals, a small fraction of the infected cells persist and divide. This reservoir persists on ART and can rekindle the infection if ART is discontinued. Because the number of possible sites of HIV DNA integration is very large, each infected cell, and all of its descendants, can be identified by the site where the provirus is integrated (IS). To understand the selective forces that determine the fates of infected cells in vivo, we compared the distribution of HIV IS in freshly-infected cells to cells from HIV-infected donors sampled both before and during ART. We found that, as has been previously reported, integration favors highly-expressed genes. However, over time the fraction of cells with proviruses integrated in highly-expressed genes decreases, implying that they grow less well. There are exceptions to this broad negative selection. When a provirus is integrated in a specific region in one of six genes, the proviruses affect the expression of the target gene, promoting growth and/or survival of the cell. Although this effect is striking, it is only a minor component of the forces that promote the growth and survival of the population of infected cells during ART.

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“…The sequencing of various transcriptomes has allowed for the identification of a plethora of noncoding RNAs (ncRNAs), corresponding to genomic regions that were previously referred to as “junk DNA” [ 52 ]. According to the latest human GENCODE release (version 28, November 2017), the human genome is composed of fewer than 20,000 protein-coding genes (i.e., a mere 2% of the total genome’s length) [ 53 ], in addition to more than 40,000 transcriptional units for previously unclassified non-protein-coding RNAs and pseudogenes ( ).…”

Section: The Family Of Alu Repeated Elements Anmentioning

confidence: 99%

ALUminating the Path of Atherosclerosis Progression: Chaos Theory Suggests a Role for Alu Repeats in the Development of Atherosclerotic Vascular Disease

Hueso

Cruzado

Navarro³

2018

IJMS

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Atherosclerosis (ATH) and coronary artery disease (CAD) are chronic inflammatory diseases with an important genetic background; they derive from the cumulative effect of multiple common risk alleles, most of which are located in genomic noncoding regions. These complex diseases behave as nonlinear dynamical systems that show a high dependence on their initial conditions; thus, long-term predictions of disease progression are unreliable. One likely possibility is that the nonlinear nature of ATH could be dependent on nonlinear correlations in the structure of the human genome. In this review, we show how chaos theory analysis has highlighted genomic regions that have shared specific structural constraints, which could have a role in ATH progression. These regions were shown to be enriched with repetitive sequences of the Alu family, genomic parasites that have colonized the human genome, which show a particular secondary structure and are involved in the regulation of gene expression. Here, we show the impact of Alu elements on the mechanisms that regulate gene expression, especially highlighting the molecular mechanisms via which the Alu elements alter the inflammatory response. We devote special attention to their relationship with the long noncoding RNA (lncRNA); antisense noncoding RNA in the INK4 locus (ANRIL), a risk factor for ATH; their role as microRNA (miRNA) sponges; and their ability to interfere with the regulatory circuitry of the (nuclear factor kappa B) NF-κB response. We aim to characterize ATH as a nonlinear dynamic system, in which small initial alterations in the expression of a number of repetitive elements are somehow amplified to reach phenotypic significance.

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Who Needs This Junk, or Genomic Dark Matter

Cited by 31 publications

References 120 publications

Integration in oncogenes plays only a minor role in determining the in vivo distribution of HIV integration sites before or during suppressive antiretroviral therapy

Integration in oncogenes plays only a minor role in determining the in vivo distribution of HIV integration sites before or during suppressive antiretroviral therapy

Integration in or Near Oncogenes Plays Only a Minor Role in Determining the in Vivo Distribution of HIV Integration Sites Before or During Suppressive Antiretroviral Therapy

ALUminating the Path of Atherosclerosis Progression: Chaos Theory Suggests a Role for Alu Repeats in the Development of Atherosclerotic Vascular Disease

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