scholarly journals Heterogeneity of transposon expression and activation of the repressive network in human fetal germ cells

2018 ◽  
Author(s):  
Boris Reznik ◽  
Steven A. Cincotta ◽  
Rebecca G. Jaszczak ◽  
Leslie J. Mateo ◽  
Joel Shen ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Nuclear Localization ◽  
Germ Cells ◽  
Epigenetic Silencing ◽  
Epigenetic Marks ◽  
Fetal Testis ◽  
Pirna Pathway

AbstractEpigenetic resetting in germ cells during development leads to the de-repression of transposable elements (TEs). piRNAs protect fetal germ cells from potentially harmful TEs by targeted destruction of mRNA and deposition of repressive epigenetic marks. Here we provide the first evidence for an active piRNA pathway and TE repression in germ cells of human fetal testis. We identify pre-pachytene piRNAs with features of secondary amplification that map most abundantly to L1 family TEs. We find that L1-ORF1p expression is heterogeneous in fetal germ cells, peaks at mid-gestation and declines concomitantly with increasing levels of piRNAs and H3K9me3, as well as nuclear localization of HIWI2. Surprisingly, following this decline, the same cells with accumulation of L1-ORF1p display highest levels of HIWI2 and H3K9me3, whereas L1-ORF1p low cells are also low in HIWI2 and H3K9me3. Conversely, earlier in development, the germ cells lacking L1-ORF1p express high levels of the chaperone HSP90a. We propose that a subset of HSP90a-armed germ cells resists L1 expression, whereas only those vulnerable L1-expressing germ cells activate the PIWI-piRNA repression pathway which leads to epigenetic silencing of L1 via H3K9me3.

scholarly journals Robust HIV-1 replication in the absence of integrase function

2020 ◽  
Author(s):  
Ishak D. Irwan ◽  
Heather L. Karnowski ◽  
Hal P. Bogerd ◽  
Kevin Tsai ◽  
Bryan R. Cullen
Keyword(s):  
Transcription Factor ◽  
Leukemia Virus ◽  
Epigenetic Silencing ◽  
Epigenetic Marks ◽  
Proviral Dna ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Circular Dnas ◽  
Episomal Dna ◽  
Hiv 1

AbstractIntegration of the proviral DNA intermediate into the host cell genome represents an essential step in the retroviral life cycle. While the reason(s) for this requirement remains unclear, it is known that unintegrated proviral DNA is epigenetically silenced. Here, we demonstrate that HIV-1 mutants lacking functional integrase can mount a robust, spreading infection in cells expressing the Tax transcription factor encoded by human T-cell leukemia virus 1. In these cells, HIV-1 forms episomal DNA circles, analogous to Hepatitis B virus covalently closed circular DNAs (cccDNAs), that are transcriptionally active and fully capable of supporting viral replication. This rescue correlates with the loss of inhibitory epigenetic marks, and the acquisition of activating marks, on histones bound to unintegrated HIV-1 DNA. Thus retroviral DNA integration may have evolved, at least in part, as a mechanism to avoid the epigenetic silencing of extrachromosomal viral DNA by host innate antiviral factors.SignificanceWhile retroviral DNA is synthesized normally after infection by integrase-deficient viruses, the resultant episomal DNA is then epigenetically silenced. Here, we show that expression of the Tax transcription factor encoded by a second human retrovirus, HTLV-1, prevents the epigenetic silencing of unintegrated HIV-1 DNA and instead induces the addition of activating epigenetic marks, and the recruitment of NF-kB/Rel proteins, to the HIV-1 LTR promoter. Moreover, in the presence of Tax, the HIV-1 DNA circles that form in the absence of integrase function are not only efficiently transcribed but also support a spreading, pathogenic IN- HIV-1 infection. Thus, retroviruses have the potential to replicate without integration, as is indeed seen with HBV.

scholarly journals Reversal of Epigenetic Silencing Allows Robust HIV-1 Replication in the Absence of Integrase Function

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Ishak D. Irwan ◽  
Heather L. Karnowski ◽  
Hal P. Bogerd ◽  
Kevin Tsai ◽  
Bryan R. Cullen
Keyword(s):  
Transcription Factor ◽  
Leukemia Virus ◽  
Epigenetic Silencing ◽  
Viral Dna ◽  
Epigenetic Marks ◽  
Proviral Dna ◽  
Human T Cell ◽  
Circular Dnas ◽  
Episomal Dna ◽  
Hiv 1

ABSTRACT Integration of the proviral DNA intermediate into the host cell genome normally represents an essential step in the retroviral life cycle. While the reason(s) for this requirement remains unclear, it is known that unintegrated proviral DNA is epigenetically silenced. Here, we demonstrate that human immunodeficiency virus 1 (HIV-1) mutants lacking a functional integrase (IN) can mount a robust, spreading infection in cells expressing the Tax transcription factor encoded by human T-cell leukemia virus 1 (HTLV-1). In these cells, HIV-1 forms episomal DNA circles, analogous to hepatitis B virus (HBV) covalently closed circular DNAs (cccDNAs), that are transcriptionally active and fully capable of supporting viral replication. In the presence of Tax, induced NF-κB proteins are recruited to the long terminal repeat (LTR) promoters present on unintegrated HIV-1 DNA, and this recruitment in turn correlates with the loss of inhibitory epigenetic marks and the acquisition of activating marks on histones bound to viral DNA. Therefore, HIV-1 is capable of replication in the absence of integrase function if the epigenetic silencing of unintegrated viral DNA can be prevented or reversed. IMPORTANCE While retroviral DNA is synthesized normally after infection by integrase-deficient viruses, the resultant episomal DNA is then epigenetically silenced. Here, we show that expression of the Tax transcription factor encoded by a second human retrovirus, HTLV-1, prevents or reverses the epigenetic silencing of unintegrated HIV-1 DNA and instead induces the addition of activating epigenetic marks and the recruitment of NF-κB/Rel proteins to the HIV-1 LTR promoter. Moreover, in the presence of Tax, the HIV-1 DNA circles that form in the absence of integrase function are not only efficiently transcribed but also support a spreading, pathogenic integrase-deficient (IN−) HIV-1 infection. Thus, retroviruses have the potential to replicate without integration, as is indeed seen with HBV. Moreover, these data suggest that integrase inhibitors may be less effective in the treatment of HIV-1 infections in individuals who are also coinfected with HTLV-1.

scholarly journals Small non-coding RNA profiling and the role of piRNA pathway genes in the protection of chicken primordial germ cells

BMC Genomics ◽  
2014 ◽  
Vol 15 (1) ◽  
pp. 757 ◽  
Author(s):  
Deivendran Rengaraj ◽  
Sang Lee ◽  
Tae Park ◽  
Hong Lee ◽  
Young Kim ◽  
...  
Keyword(s):  
Germ Cells ◽  
Primordial Germ Cells ◽  
Rna Profiling ◽  
Non Coding Rna ◽  
Pirna Pathway

Mammalian genome evolution as a result of epigenetic regulation of transposable elements

2014 ◽  
Vol 5 (3) ◽  
pp. 183-194 ◽  
Author(s):  
Reuben M. Buckley ◽  
David L. Adelson
Keyword(s):  
Gene Expression ◽  
Transposable Elements ◽  
Epigenetic Regulation ◽  
Dna Sequences ◽  
Defense Mechanisms ◽  
Regulatory Networks ◽  
Regulation Of Gene Expression ◽  
Epigenetic Marks ◽  
Rna Molecules ◽  
Mammalian Genomes

AbstractTransposable elements (TEs) make up a large proportion of mammalian genomes and are a strong evolutionary force capable of rewiring regulatory networks and causing genome rearrangements. Additionally, there are many eukaryotic epigenetic defense mechanisms able to transcriptionally silence TEs. Furthermore, small RNA molecules that target TE DNA sequences often mediate these epigenetic defense mechanisms. As a result, epigenetic marks associated with TE silencing can be reestablished after epigenetic reprogramming – an event during the mammalian life cycle that results in widespread loss of parental epigenetic marks. Furthermore, targeted epigenetic marks associated with TE silencing may have an impact on nearby gene expression. Therefore, TEs may have driven species evolution via their ability to heritably alter the epigenetic regulation of gene expression in mammals.

Small RNAs from a Big Genome: The piRNA Pathway and Transposable Elements in the Salamander Species Desmognathus fuscus

2016 ◽  
Vol 83 (3-4) ◽  
pp. 126-136 ◽  
Author(s):  
M. J. Madison-Villar ◽  
Cheng Sun ◽  
Nelson C. Lau ◽  
Matthew L. Settles ◽  
Rachel Lockridge Mueller
Keyword(s):  
Transposable Elements ◽  
Small Rnas ◽  
Pirna Pathway ◽  
Salamander Species

scholarly journals Nuclear localization, DNA binding and restricted expression in neural and germ cells of zebrafish Dmrt3

2008 ◽  
Vol 100 (8) ◽  
pp. 453-463 ◽  
Author(s):  
Qin Li ◽  
Xiang Zhou ◽  
Yiqing Guo ◽  
Xuan Shang ◽  
Hao Chen ◽  
...  
Keyword(s):  
Dna Binding ◽  
Nuclear Localization ◽  
Germ Cells

scholarly journals Knockout Gene-Based Evidence for PIWI-Interacting RNA Pathway in Mammals

2021 ◽  
Vol 9 ◽  
Author(s):  
Yinuo Li ◽  
Yue Zhang ◽  
Mingxi Liu
Keyword(s):  
Germ Cells ◽  
Current Knowledge ◽  
Conditional Knockout ◽  
Evolutionarily Conserved ◽  
Cell Arrest ◽  
And Function ◽  
Knockout Animals ◽  
Pirna Pathway ◽  
Long Interspersed Nuclear Element ◽  
Knockout Gene

The PIWI-interacting RNA (piRNA) pathway mainly consists of evolutionarily conserved protein factors. Intriguingly, many mutations of piRNA pathway factors lead to meiotic arrest during spermatogenesis. The majority of piRNA factor-knockout animals show arrested meiosis in spermatogenesis, and only a few show post-meiosis male germ cell arrest. It is still unclear whether the majority of piRNA factors expressed in spermatids are involved in long interspersed nuclear element-1 repression after meiosis, but future conditional knockout research is expected to resolve this. In addition, recent hamster knockout studies showed that a piRNA factor is necessary for oocytes—in complete contrast to the findings in mice. This species discrepancy allows researchers to reexamine the function of piRNA in female germ cells. This mini-review focuses on the current knowledge of protein factors derived from mammalian knockout studies and summarizes their roles in the biogenesis and function of piRNAs.

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