Physiological and Pathological Transcriptional Activation of Endogenous Retroelements Assessed by RNA-Sequencing of B Lymphocytes

In addition to evolutionarily-accrued sequence mutation or deletion, endogenous retroelements (EREs) in eukaryotic genomes are subject to epigenetic silencing, preventing or reducing their transcription, particularly in the germplasm. Nevertheless, transcriptional activation of EREs, including endog...

Täydet tiedot

Bibliografiset tiedot
Päätekijät: Jan Attig, George R. Young, Jonathan P. Stoye, George Kassiotis
Aineistotyyppi: Artikkeli
Kieli:English
Julkaistu: Frontiers Media S.A. 2017-12-01
Sarja:Frontiers in Microbiology
Aiheet:
Linkit:http://journal.frontiersin.org/article/10.3389/fmicb.2017.02489/full
_version_ 1828526816423313408
author Jan Attig
George R. Young
Jonathan P. Stoye
Jonathan P. Stoye
George Kassiotis
George Kassiotis
author_facet Jan Attig
George R. Young
Jonathan P. Stoye
Jonathan P. Stoye
George Kassiotis
George Kassiotis
author_sort Jan Attig
collection DOAJ
description In addition to evolutionarily-accrued sequence mutation or deletion, endogenous retroelements (EREs) in eukaryotic genomes are subject to epigenetic silencing, preventing or reducing their transcription, particularly in the germplasm. Nevertheless, transcriptional activation of EREs, including endogenous retroviruses (ERVs) and long interspersed nuclear elements (LINEs), is observed in somatic cells, variably upon cellular differentiation and frequently upon cellular transformation. ERE transcription is modulated during physiological and pathological immune cell activation, as well as in immune cell cancers. However, our understanding of the potential consequences of such modulation remains incomplete, partly due to the relative scarcity of information regarding genome-wide ERE transcriptional patterns in immune cells. Here, we describe a methodology that allows probing RNA-sequencing (RNA-seq) data for genome-wide expression of EREs in murine and human cells. Our analysis of B cells reveals that their transcriptional response during immune activation is dominated by induction of gene transcription, and that EREs respond to a much lesser extent. The transcriptional activity of the majority of EREs is either unaffected or reduced by B cell activation both in mice and humans, albeit LINEs appear considerably more responsive in the latter host. Nevertheless, a small number of highly distinct ERVs are strongly and consistently induced during B cell activation. Importantly, this pattern contrasts starkly with B cell transformation, which exhibits widespread induction of EREs, including ERVs that minimally overlap with those responsive to immune stimulation. The distinctive patterns of ERE induction suggest different underlying mechanisms and will help separate physiological from pathological expression.
first_indexed 2024-12-11T21:30:25Z
format Article
id doaj.art-65b8f0d068eb4fcdbc5ac238e9b13d6f
institution Directory Open Access Journal
issn 1664-302X
language English
last_indexed 2024-12-11T21:30:25Z
publishDate 2017-12-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Microbiology
spelling doaj.art-65b8f0d068eb4fcdbc5ac238e9b13d6f2022-12-22T00:50:12ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2017-12-01810.3389/fmicb.2017.02489315139Physiological and Pathological Transcriptional Activation of Endogenous Retroelements Assessed by RNA-Sequencing of B LymphocytesJan Attig0George R. Young1Jonathan P. Stoye2Jonathan P. Stoye3George Kassiotis4George Kassiotis5Retroviral Immunology, The Francis Crick Institute, London, United KingdomRetrovirus-Host Interactions, The Francis Crick Institute, London, United KingdomRetrovirus-Host Interactions, The Francis Crick Institute, London, United KingdomDepartment of Medicine, Faculty of Medicine, Imperial College London, London, United KingdomRetroviral Immunology, The Francis Crick Institute, London, United KingdomDepartment of Medicine, Faculty of Medicine, Imperial College London, London, United KingdomIn addition to evolutionarily-accrued sequence mutation or deletion, endogenous retroelements (EREs) in eukaryotic genomes are subject to epigenetic silencing, preventing or reducing their transcription, particularly in the germplasm. Nevertheless, transcriptional activation of EREs, including endogenous retroviruses (ERVs) and long interspersed nuclear elements (LINEs), is observed in somatic cells, variably upon cellular differentiation and frequently upon cellular transformation. ERE transcription is modulated during physiological and pathological immune cell activation, as well as in immune cell cancers. However, our understanding of the potential consequences of such modulation remains incomplete, partly due to the relative scarcity of information regarding genome-wide ERE transcriptional patterns in immune cells. Here, we describe a methodology that allows probing RNA-sequencing (RNA-seq) data for genome-wide expression of EREs in murine and human cells. Our analysis of B cells reveals that their transcriptional response during immune activation is dominated by induction of gene transcription, and that EREs respond to a much lesser extent. The transcriptional activity of the majority of EREs is either unaffected or reduced by B cell activation both in mice and humans, albeit LINEs appear considerably more responsive in the latter host. Nevertheless, a small number of highly distinct ERVs are strongly and consistently induced during B cell activation. Importantly, this pattern contrasts starkly with B cell transformation, which exhibits widespread induction of EREs, including ERVs that minimally overlap with those responsive to immune stimulation. The distinctive patterns of ERE induction suggest different underlying mechanisms and will help separate physiological from pathological expression.http://journal.frontiersin.org/article/10.3389/fmicb.2017.02489/fullendogenous retrovirusesendogenous retroelementstranscriptiongeneticB lymphocyte activationB cell lymphoma
spellingShingle Jan Attig
George R. Young
Jonathan P. Stoye
Jonathan P. Stoye
George Kassiotis
George Kassiotis
Physiological and Pathological Transcriptional Activation of Endogenous Retroelements Assessed by RNA-Sequencing of B Lymphocytes
Frontiers in Microbiology
endogenous retroviruses
endogenous retroelements
transcription
genetic
B lymphocyte activation
B cell lymphoma
title Physiological and Pathological Transcriptional Activation of Endogenous Retroelements Assessed by RNA-Sequencing of B Lymphocytes
title_full Physiological and Pathological Transcriptional Activation of Endogenous Retroelements Assessed by RNA-Sequencing of B Lymphocytes
title_fullStr Physiological and Pathological Transcriptional Activation of Endogenous Retroelements Assessed by RNA-Sequencing of B Lymphocytes
title_full_unstemmed Physiological and Pathological Transcriptional Activation of Endogenous Retroelements Assessed by RNA-Sequencing of B Lymphocytes
title_short Physiological and Pathological Transcriptional Activation of Endogenous Retroelements Assessed by RNA-Sequencing of B Lymphocytes
title_sort physiological and pathological transcriptional activation of endogenous retroelements assessed by rna sequencing of b lymphocytes
topic endogenous retroviruses
endogenous retroelements
transcription
genetic
B lymphocyte activation
B cell lymphoma
url http://journal.frontiersin.org/article/10.3389/fmicb.2017.02489/full
work_keys_str_mv AT janattig physiologicalandpathologicaltranscriptionalactivationofendogenousretroelementsassessedbyrnasequencingofblymphocytes
AT georgeryoung physiologicalandpathologicaltranscriptionalactivationofendogenousretroelementsassessedbyrnasequencingofblymphocytes
AT jonathanpstoye physiologicalandpathologicaltranscriptionalactivationofendogenousretroelementsassessedbyrnasequencingofblymphocytes
AT jonathanpstoye physiologicalandpathologicaltranscriptionalactivationofendogenousretroelementsassessedbyrnasequencingofblymphocytes
AT georgekassiotis physiologicalandpathologicaltranscriptionalactivationofendogenousretroelementsassessedbyrnasequencingofblymphocytes
AT georgekassiotis physiologicalandpathologicaltranscriptionalactivationofendogenousretroelementsassessedbyrnasequencingofblymphocytes