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Article ; Online: The methyltransferase Setdb1 is essential for meiosis and mitosis in mouse oocytes and early embryos.

Eymery, Angeline / Liu, Zichuan / Ozonov, Evgeniy A / Stadler, Michael B / Peters, Antoine H F M

2016 Volume 143, Issue 15, Page(s) 2767–2779

Abstract: Oocytes develop the competence for meiosis and early embryogenesis during their growth. Setdb1 is a histone H3 lysine 9 (H3K9) methyltransferase required for post-implantation development and has been implicated in the transcriptional silencing of genes ... ...

Abstract	Oocytes develop the competence for meiosis and early embryogenesis during their growth. Setdb1 is a histone H3 lysine 9 (H3K9) methyltransferase required for post-implantation development and has been implicated in the transcriptional silencing of genes and endogenous retroviral elements (ERVs). To address its role in oogenesis and pre-implantation development, we conditionally deleted Setdb1 in growing oocytes. Loss of Setdb1 expression greatly impaired meiosis. It delayed meiotic resumption, altered the dynamics of chromatin condensation, and impaired kinetochore-spindle interactions, bipolar spindle organization and chromosome segregation in more mature oocytes. The observed phenotypes related to changes in abundance of specific transcripts in mutant oocytes. Setdb1 maternally deficient embryos arrested during pre-implantation development and showed comparable defects during cell cycle progression and in chromosome segregation. Finally, transcriptional profiling data indicate that Setdb1 downregulates rather than silences expression of ERVK and ERVL-MaLR retrotransposons and associated chimearic transcripts during oogenesis. Our results identify Setdb1 as a newly discovered meiotic and embryonic competence factor safeguarding genome integrity at the onset of life.
MeSH term(s)	Animals ; Chromosome Segregation/genetics ; Chromosome Segregation/physiology ; Embryonic Development/genetics ; Embryonic Development/physiology ; Female ; Histone-Lysine N-Methyltransferase/genetics ; Histone-Lysine N-Methyltransferase/metabolism ; Kinetochores/metabolism ; Male ; Meiosis/genetics ; Meiosis/physiology ; Mice ; Mitosis/genetics ; Mitosis/physiology ; Oocytes/cytology ; Oocytes/metabolism ; Oogenesis/genetics ; Oogenesis/physiology ; Retroelements/genetics ; Retroelements/physiology
Chemical Substances	Retroelements ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43) ; SETDB1 protein, mouse (EC 2.1.1.43)
Language	English
Publishing date	2016--01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.132746
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Article ; Online: The secret message of heterochromatin: new insights into the mechanisms and function of centromeric and pericentric repeat sequence transcription.

Eymery, Angeline / Callanan, Mary / Vourc'h, Claire

The International journal of developmental biology

2009 Volume 53, Issue 2-3, Page(s) 259–268

Abstract: In the fission yeast, S. Pombe, small dsRNA generated by RNAi-dependent mechanisms are involved in the establishment and maintenance of heterochromatic regions. The existence of conserved features within the general organization of centromeric and ... ...

Abstract	In the fission yeast, S. Pombe, small dsRNA generated by RNAi-dependent mechanisms are involved in the establishment and maintenance of heterochromatic regions. The existence of conserved features within the general organization of centromeric and pericentromeric repeats in yeast, mouse and human argues in favor of a conserved role for centromeric and pericentromeric-derived transcripts across these species. In support of this, evidence is accumulating that centromeric and pericentromeric sequences are transcriptionally competent in diverse biological contexts in mammalian cells. Given the importance of centromeric and pericentromeric regions, not only with respect to centromere function, but also to gene regulation, this review examines the biological contexts in which mouse and human centromeric and pericentromeric-specific transcripts have been observed. The structure of the transcripts generated, the molecular mechanisms underlying their expression and their supposed functions will be discussed.
MeSH term(s)	Animals ; Base Sequence ; Centromere/genetics ; Gene Expression Regulation ; Heterochromatin/genetics ; Humans ; Models, Biological ; Molecular Sequence Data ; Repetitive Sequences, Nucleic Acid/genetics ; Transcription, Genetic
Chemical Substances	Heterochromatin
Language	English
Publishing date	2009
Publishing country	Spain
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1036070-0
ISSN	1696-3547 ; 0214-6282
ISSN (online)	1696-3547
ISSN	0214-6282
DOI	10.1387/ijdb.082673ae
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Zs.A 3202: Show issues

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Article ; Online: "Dot COM", a nuclear transit center for the primary piRNA pathway in Drosophila.

Dennis, Cynthia / Zanni, Vanessa / Brasset, Emilie / Eymery, Angeline / Zhang, Liang / Mteirek, Rana / Jensen, Silke / Rong, Yikang S / Vaury, Chantal

PloS one

2013 Volume 8, Issue 9, Page(s) e72752

Abstract: The piRNA pathway protects genomes by silencing mobile elements. Despite advances in understanding the processing events that generate piRNAs for silencing, little is known about how primary transcripts are transported from their genomic clusters to ... ...

Abstract	The piRNA pathway protects genomes by silencing mobile elements. Despite advances in understanding the processing events that generate piRNAs for silencing, little is known about how primary transcripts are transported from their genomic clusters to their processing centers. Using a model of the Drosophila COM/flamenco locus in ovarian somatic cells, we identified a prominent nuclear structure called Dot COM, which is enriched in long transcripts from piRNA clusters but located far from their transcription sites. Remarkably, transcripts from multiple clusters accumulate at Dot COM, which is often juxtaposed with Yb-bodies, the cytoplasmic processing centers for cluster transcripts. Genetic evidence suggests that the accumulation of precursor transcripts at Dot COM represents one of the most upstream events in the piRNA pathway. Our results provide new insights into the initial steps of the piRNA pathway, and open up a new research area important for a complete understanding of this conserved pathway.
MeSH term(s)	Animals ; Cell Nucleus/metabolism ; Cytoplasm/genetics ; Cytoplasm/metabolism ; Drosophila/genetics ; Drosophila/metabolism ; Female ; Genetic Loci ; Multigene Family ; Ovarian Follicle/cytology ; Ovarian Follicle/metabolism ; RNA Transport ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Transcription, Genetic
Chemical Substances	RNA, Small Interfering
Language	English
Publishing date	2013-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0072752
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Article ; Online: "Dot COM", a nuclear transit center for the primary piRNA pathway in Drosophila.

Cynthia Dennis / Vanessa Zanni / Emilie Brasset / Angeline Eymery / Liang Zhang / Rana Mteirek / Silke Jensen / Yikang S Rong / Chantal Vaury

PLoS ONE, Vol 8, Iss 9, p e

2013 Volume 72752

Abstract	The piRNA pathway protects genomes by silencing mobile elements. Despite advances in understanding the processing events that generate piRNAs for silencing, little is known about how primary transcripts are transported from their genomic clusters to their processing centers. Using a model of the Drosophila COM/flamenco locus in ovarian somatic cells, we identified a prominent nuclear structure called Dot COM, which is enriched in long transcripts from piRNA clusters but located far from their transcription sites. Remarkably, transcripts from multiple clusters accumulate at Dot COM, which is often juxtaposed with Yb-bodies, the cytoplasmic processing centers for cluster transcripts. Genetic evidence suggests that the accumulation of precursor transcripts at Dot COM represents one of the most upstream events in the piRNA pathway. Our results provide new insights into the initial steps of the piRNA pathway, and open up a new research area important for a complete understanding of this conserved pathway.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Heat shock factor 1 binds to and transcribes satellite II and III sequences at several pericentromeric regions in heat-shocked cells.

Eymery, Angéline / Souchier, Catherine / Vourc'h, Claire / Jolly, Caroline

Experimental cell research

2010 Volume 316, Issue 11, Page(s) 1845–1855

Abstract: Cells respond to stress by activating the synthesis of heat shock proteins (HSPs) which protect the cells against the deleterious effects of stress. This mechanism is controlled by the heat shock factor 1 (HSF1). In parallel to HSP gene transcription, in ...

Abstract	Cells respond to stress by activating the synthesis of heat shock proteins (HSPs) which protect the cells against the deleterious effects of stress. This mechanism is controlled by the heat shock factor 1 (HSF1). In parallel to HSP gene transcription, in human cells, HSF1 also binds to and transcribes satellite III repeated sequences present in numerous copies in the 9q12 pericentromeric region of chromosome 9. These HSF1 accumulation sites are termed nuclear stress bodies (nSBs). In tumor cells, however, the number of nSBs is higher than the number of 9q12 copies, suggesting the existence of other HSF1 targets. In this paper, we were interested in characterizing these other HSF1 binding sites. We show that HSF1 indeed binds to the pericentromeric region of 14 chromosomes, thereby directing the formation of 'secondary nSBs'. The appearance of secondary nSBs depends on the number of satellite sequences present in the target locus, and on the cellular amount of HSF1 protein. Moreover, secondary nSBs also correspond to transcription sites, thus demonstrating that heat shock induces a genome-wide transcription of satellite sequences. Finally, by analyzing published transcriptomic data, we show that the derepression of these large heterochromatic blocks does not significantly affect the transcription of neighboring genes.
MeSH term(s)	Animals ; Binding Sites/genetics ; Cell Line ; Centromere/genetics ; Centromere/metabolism ; Chromosomes, Human/genetics ; Chromosomes, Human/metabolism ; DNA Primers/genetics ; DNA, Satellite/genetics ; DNA, Satellite/metabolism ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; HeLa Cells ; Heat Shock Transcription Factors ; Heat-Shock Response/genetics ; Heat-Shock Response/physiology ; Humans ; Hybrid Cells ; In Situ Hybridization, Fluorescence ; Mice ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcription, Genetic
Chemical Substances	DNA Primers ; DNA, Satellite ; DNA-Binding Proteins ; HSF1 protein, human ; Heat Shock Transcription Factors ; Hsf1 protein, mouse ; Recombinant Fusion Proteins ; Transcription Factors
Language	English
Publishing date	2010-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1493-x
ISSN	1090-2422 ; 0014-4827
ISSN (online)	1090-2422
ISSN	0014-4827
DOI	10.1016/j.yexcr.2010.02.002
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Zs.A 563: Show issues

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Article ; Online: Distribution, evolution, and diversity of retrotransposons at the flamenco locus reflect the regulatory properties of piRNA clusters.

Zanni, Vanessa / Eymery, Angéline / Coiffet, Michael / Zytnicki, Matthias / Luyten, Isabelle / Quesneville, Hadi / Vaury, Chantal / Jensen, Silke

Proceedings of the National Academy of Sciences of the United States of America

2013 Volume 110, Issue 49, Page(s) 19842–19847

Abstract: Most of our understanding of Drosophila heterochromatin structure and evolution has come from the annotation of heterochromatin from the isogenic y; cn bw sp strain. However, almost nothing is known about the heterochromatin's structural dynamics and ... ...

Abstract	Most of our understanding of Drosophila heterochromatin structure and evolution has come from the annotation of heterochromatin from the isogenic y; cn bw sp strain. However, almost nothing is known about the heterochromatin's structural dynamics and evolution. Here, we focus on a 180-kb heterochromatic locus producing Piwi-interacting RNAs (piRNA cluster), the flamenco (flam) locus, known to be responsible for the control of at least three transposable elements (TEs). We report its detailed structure in three different Drosophila lines chosen according to their capacity to repress or not to repress the expression of two retrotransposons named ZAM and Idefix, and we show that they display high structural diversity. Numerous rearrangements due to homologous and nonhomologous recombination, deletions and segmental duplications, and loss and gain of TEs are diverse sources of active genomic variation at this locus. Notably, we evidence a correlation between the presence of ZAM and Idefix in this piRNA cluster and their silencing. They are absent from flam in the strain where they are derepressed. We show that, unexpectedly, more than half of the flam locus results from recent TE insertions and that most of the elements concerned are prone to horizontal transfer between species of the melanogaster subgroup. We build a model showing how such high and constant dynamics of a piRNA master locus open the way to continual emergence of new patterns of piRNA biogenesis leading to changes in the level of transposition control.
MeSH term(s)	Animals ; Base Sequence ; Cadherins/genetics ; Computational Biology ; Drosophila Proteins/genetics ; Drosophila melanogaster/genetics ; Evolution, Molecular ; Gene Transfer, Horizontal/genetics ; Genetic Variation ; Heterochromatin/genetics ; Molecular Sequence Data ; Oligonucleotides/genetics ; RNA Interference ; RNA, Small Interfering/genetics ; Retroelements/genetics ; Sequence Alignment ; Sequence Analysis, DNA
Chemical Substances	Cadherins ; Drosophila Proteins ; Heterochromatin ; Oligonucleotides ; RNA, Small Interfering ; Retroelements ; stan protein, Drosophila
Language	English
Publishing date	2013-11-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1313677110
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Zs.A 1148: Show issues

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Article ; Online: Global analysis of DNA methylation and transcription of human repetitive sequences.

Horard, Béatrice / Eymery, Angéline / Fourel, Geneviève / Vassetzky, Nikita / Puechberty, Jacques / Roizes, Gérard / Lebrigand, Kevin / Barbry, Pascal / Laugraud, Aurélie / Gautier, Christian / Simon, Elsa Ben / Devaux, Frédéric / Magdinier, Frédérique / Vourc'h, Claire / Gilson, Eric

Epigenetics

2009 Volume 4, Issue 5, Page(s) 339–350

Abstract: Half of the human genome consists of repetitive DNA sequences. Recent studies in various organisms highlight the role of chromatin regulation of repetitive DNA in gene regulation as well as in maintainance of chromosomes and genome integrity. Hence, ... ...

Abstract	Half of the human genome consists of repetitive DNA sequences. Recent studies in various organisms highlight the role of chromatin regulation of repetitive DNA in gene regulation as well as in maintainance of chromosomes and genome integrity. Hence, repetitive DNA sequences might be potential "sensors" for chromatin changes associated with pathogenesis. Therefore, we developed a new genomic tool called RepArray. RepArray is a repeat-specific microarray composed of a representative set of human repeated sequences including transposon-derived repeats, simple sequences repeats, tandemly repeated sequences such as centromeres and telomeres. We showed that combined to anti-methylcytosine immunoprecipitation assay, the RepArray can be used to generate repeat-specific methylation maps. Using cell lines impaired chemically or genetically for DNA methyltransferases activities, we were able to distinguish different epigenomes demonstrating that repeats can be used as markers of genome-wide methylation changes. Besides, using a well-documented system model, the thermal stress, we demonstrated that RepArray is also a fast and reliable tool to obtain an overview of overall transcriptional activity on whole repetitive compartment in a given cell type. Thus, the RepArray represents the first valuable tool for systematic and genome-wide analyses of the methylation and transcriptional status of the repetitive counterpart of the human genome.
MeSH term(s)	Azacitidine/pharmacology ; DNA Methylation/drug effects ; DNA Probes/metabolism ; Gene Expression Profiling ; HCT116 Cells ; HeLa Cells ; Humans ; Oligonucleotide Array Sequence Analysis ; Principal Component Analysis ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Repetitive Sequences, Nucleic Acid/genetics ; Reproducibility of Results ; Transcription, Genetic/drug effects
Chemical Substances	DNA Probes ; RNA, Messenger ; Azacitidine (M801H13NRU)
Language	English
Publishing date	2009-07-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1559-2308
ISSN (online)	1559-2308
DOI	10.4161/epi.4.5.9284
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Article ; Online: A transcriptomic analysis of human centromeric and pericentric sequences in normal and tumor cells.

Eymery, Angéline / Horard, Béatrice / El Atifi-Borel, Michèle / Fourel, Geneviève / Berger, François / Vitte, Anne-Laure / Van den Broeck, Arnaud / Brambilla, Elisabeth / Fournier, Alexandra / Callanan, Mary / Gazzeri, Sylvie / Khochbin, Saadi / Rousseaux, Sophie / Gilson, Eric / Vourc'h, Claire

Nucleic acids research

2009 Volume 37, Issue 19, Page(s) 6340–6354

Abstract: Although there is now evidence that the expression of centromeric (CT) and pericentric (PCT) sequences are key players in major genomic functions, their transcriptional status in human cells is still poorly known. The main reason for this lack of data is ...

Abstract	Although there is now evidence that the expression of centromeric (CT) and pericentric (PCT) sequences are key players in major genomic functions, their transcriptional status in human cells is still poorly known. The main reason for this lack of data is the complexity and high level of polymorphism of these repeated sequences, which hampers straightforward analyses by available transcriptomic approaches. Here a transcriptomic macro-array dedicated to the analysis of CT and PCT expression is developed and validated in heat-shocked (HS) HeLa cells. For the first time, the expression status of CT and PCT sequences is analyzed in a series of normal and cancer human cells and tissues demonstrating that they are repressed in all normal tissues except in the testis, where PCT transcripts are found. Moreover, PCT sequences are specifically expressed in HS cells in a Heat-Shock Factor 1 (HSF1)-dependent fashion, and we show here that another independent pathway, involving DNA hypo-methylation, can also trigger their expression. Interestingly, CT and PCT were found illegitimately expressed in somatic cancer samples, whereas PCT were repressed in testis cancer, suggesting that the expression of CT and PCT sequences may represent a good indicator of epigenetic deregulations occurring in response to environmental changes or in cell transformation.
MeSH term(s)	Cell Line, Tumor ; Centromere/chemistry ; Centromere/metabolism ; Chromatin Assembly and Disassembly ; Gene Expression Profiling ; HeLa Cells ; Heat-Shock Response ; Humans ; Oligonucleotide Array Sequence Analysis ; Ribonuclease III/metabolism
Chemical Substances	Ribonuclease III (EC 3.1.26.3)
Language	English
Publishing date	2009-08-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkp639
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Zs.A 1067: Show issues

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Article: Distribution, evolution, and diversity of retrotransposons at the flamenco locus reflect the regulatory properties of piRNA clusters

Zanni, Vanessa / Eymery, Angéline / Coiffet, Michael / Zytnicki, Matthias / Luyten, Isabelle / Quesneville, Hadi / Vaury, Chantal / Jensen, Silke

Proceedings of the National Academy of Sciences of the United States of America , . (2013)

Abstract	Most of our understanding of Drosophila heterochromatin structure and evolution has come from the annotation of heterochromatin from the isogenic y; cn bw sp strain. However, almost nothing is known about the heterochromatin's structural dynamics and evolution. Here, we focus on a 180-kb heterochromatic locus producing Piwi-interacting RNAs (piRNA cluster), the flamenco (flam) locus, known to be responsible for the control of at least three transposable elements (TEs). We report its detailed structure in three different Drosophila lines chosen according to their capacity to repress or not to repress the expression of two retrotransposons named ZAM and Idefix, and we show that they display high structural diversity. Numerous rearrangements due to homologous and nonhomologous recombination, deletions and segmental duplications, and loss and gain of TEs are diverse sources of active genomic variation at this locus. Notably, we evidence a correlation between the presence of ZAM and Idefix in this piRNA cluster and their silencing. They are absent from flam in the strain where they are derepressed. We show that, unexpectedly, more than half of the flam locus results from recent TE insertions and that most of the elements concerned are prone to horizontal transfer between species of the melanogaster subgroup. We build a model showing how such high and constant dynamics of a piRNA master locus open the way to continual emergence of new patterns of piRNA biogenesis leading to changes in the level of transposition control.
Language	English
Document type	Article
Database	AGRIS - International Information System for the Agricultural Sciences and Technology

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Article: Distribution, evolution, and diversity of retrotransposons at the flamenco locus reflect the regulatory properties of piRNA clusters

Zanni, Vanessa / Eymery, Angéline / Coiffet, Michael / Zytnicki, Matthias / Luyten, Isabelle / Quesneville, Hadi / Vaury, Chantal / Jensen, Silke

Proceedings of the National Academy of Sciences of the United States of America , . (2013)

Abstract	Most of our understanding of Drosophila heterochromatin structure and evolution has come from the annotation of heterochromatin from the isogenic y; cn bw sp strain. However, almost nothing is known about the heterochromatin's structural dynamics and evolution. Here, we focus on a 180-kb heterochromatic locus producing Piwi-interacting RNAs (piRNA cluster), the flamenco (flam) locus, known to be responsible for the control of at least three transposable elements (TEs). We report its detailed structure in three different Drosophila lines chosen according to their capacity to repress or not to repress the expression of two retrotransposons named ZAM and Idefix, and we show that they display high structural diversity. Numerous rearrangements due to homologous and nonhomologous recombination, deletions and segmental duplications, and loss and gain of TEs are diverse sources of active genomic variation at this locus. Notably, we evidence a correlation between the presence of ZAM and Idefix in this piRNA cluster and their silencing. They are absent from flam in the strain where they are derepressed. We show that, unexpectedly, more than half of the flam locus results from recent TE insertions and that most of the elements concerned are prone to horizontal transfer between species of the melanogaster subgroup. We build a model showing how such high and constant dynamics of a piRNA master locus open the way to continual emergence of new patterns of piRNA biogenesis leading to changes in the level of transposition control.
Language	English
Document type	Article
Database	AGRIS - International Information System for the Agricultural Sciences and Technology

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