Activation of HERV-K(HML-2) disrupts cortical patterning and neuronal differentiation by increasing NTRK3

Nair, Vidya Padmanabhan; Liu, Hengyuan; Ciceri, Gabriele; Jungverdorben, Johannes; Frishman, Goar; Tchieu, Jason; Cederquist, Gustav Y.; Rothenaigner, Ina; Schorpp, Kenji; Klepper, Lena; Walsh, Ryan; Kim, Tae Wan; Cornacchia, Daniela; Ruepp, Andreas; Mayer, Jens; Hadian, Kamyar; Frishman, Dmitrij; Studer, Lorenz; Vincendeau, Michelle

doi:10.1016/j.stem.2021.04.009

Cited by 34 publications

(12 citation statements)

References 83 publications

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“…HERVs are involved in various biological processes through encoding proteins, acting as promoters/enhancers, or lncRNAs to affect human health and disease. In addition to the discoveries mentioned above, HERVs are also involved in neurodevelopment [104] , [105] , HIV-1 infection [106] , chronic hepatitis C virus (HCV) infection [107] , and type 1 diabetes [108] , [109] . Although there are a large number of studies focusing on the expression of whole HERVs families, most of these works did not detect the individual coordinates of the expressed loci, or measure the expression of a single locus.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Human endogenous retroviruses in development and disease

Mao

Zhang

Cong

2021

Computational and Structural Biotechnology Journal

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Section: Conclusion and Perspectivementioning

confidence: 99%

Human endogenous retroviruses in development and disease

Mao

Zhang

Cong

2021

Computational and Structural Biotechnology Journal

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“…LTR promoter of HERV-K is activated in hESCs by the CRISPR activation (CRISPRa) method ( Padmanabhan Nair et al, 2021 ). HERV-K activated hESCs are differentiated into cortical neurons.…”

Section: Molecular and Cellular Events Controlled By Herv Elementsmentioning

confidence: 99%

“…Moreover, the long terminal repeats (LTRs) of HERVs affect gene expression by interacting with a variety of endogenous transcription factors, influencing biological processes such as early embryogenesis ( Fuentes et al, 2018 ) or innate immunity ( Chuong et al, 2016 ). Elevated transcription driven by HERV LTRs can disrupt neuronal differentiation, which indicates that HERV activation may play a critical role in brain development ( Padmanabhan Nair et al, 2021 ). LTR-overlapping transcripts specific in certain cancers raises the possibility that the highly predictable transcripts can provide disease prognosis and information of cancer-specific antigenicity ( Attig et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Human Endogenous Retroviruses as Gene Expression Regulators: Insights from Animal Models into Human Diseases

Durnaoglu

Lee

Ahnn

2021

Molecules and Cells

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The human genome contains many retroviral elements called human endogenous retroviruses (HERVs), resulting from the integration of retroviruses throughout evolution. HERVs once were considered inactive junk because they are not replication-competent, primarily localized in the heterochromatin, and silenced by methylation. But HERVs are now clearly shown to actively regulate gene expression in various physiological and pathological conditions such as developmental processes, immune regulation, cancers, autoimmune diseases, and neurological disorders. Recent studies report that HERVs are activated in patients suffering from coronavirus disease 2019 (COVID-19), the current pandemic caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. In this review, we describe internal and external factors that influence HERV activities. We also present evidence showing the gene regulatory activity of HERV LTRs (long terminal repeats) in model organisms such as mice, rats, zebrafish, and invertebrate models of worms and flies. Finally, we discuss several molecular and cellular pathways involving various transcription factors and receptors, through which HERVs affect downstream cellular and physiological events such as epigenetic modifications, calcium influx, protein phosphorylation, and cytokine release. Understanding how HERVs participate in various physiological and pathological processes will help develop a strategy to generate effective therapeutic approaches targeting HERVs.

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“…HERV expression is tightly regulated during development, and increased transcription of HERVk is detrimental for the development and function of cortical neurons in human-pluripotent-stem-cell-based systems [ 97 ]. LINE1 is also implicated as a heritable genetic contributor to somatic mosaicism via CNV formation.…”

Section: Retrotransposonsmentioning

confidence: 99%

Genomic Mosaicism Formed by Somatic Variation in the Aging and Diseased Brain

Costantino

Nicodemus

Chun

2021

Genes

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Over the past 20 years, analyses of single brain cell genomes have revealed that the brain is composed of cells with myriad distinct genomes: the brain is a genomic mosaic, generated by a host of DNA sequence-altering processes that occur somatically and do not affect the germline. As such, these sequence changes are not heritable. Some processes appear to occur during neurogenesis, when cells are mitotic, whereas others may also function in post-mitotic cells. Here, we review multiple forms of DNA sequence alterations that have now been documented: aneuploidies and aneusomies, smaller copy number variations (CNVs), somatic repeat expansions, retrotransposons, genomic cDNAs (gencDNAs) associated with somatic gene recombination (SGR), and single nucleotide variations (SNVs). A catch-all term of DNA content variation (DCV) has also been used to describe the overall phenomenon, which can include multiple forms within a single cell’s genome. A requisite step in the analyses of genomic mosaicism is ongoing technology development, which is also discussed. Genomic mosaicism alters one of the most stable biological molecules, DNA, which may have many repercussions, ranging from normal functions including effects of aging, to creating dysfunction that occurs in neurodegenerative and other brain diseases, most of which show sporadic presentation, unlinked to causal, heritable genes.

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Activation of HERV-K(HML-2) disrupts cortical patterning and neuronal differentiation by increasing NTRK3

Cited by 34 publications

References 83 publications

Human endogenous retroviruses in development and disease

Human endogenous retroviruses in development and disease

Human Endogenous Retroviruses as Gene Expression Regulators: Insights from Animal Models into Human Diseases

Genomic Mosaicism Formed by Somatic Variation in the Aging and Diseased Brain

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