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  1. Article ; Online: Imprints in the history of epigenetics.

    Kelsey, Gavin

    Nature reviews. Molecular cell biology

    2020  Volume 21, Issue 10, Page(s) 566–567

    Language English
    Publishing date 2020-07-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 2031313-5
    ISSN 1471-0080 ; 1471-0072
    ISSN (online) 1471-0080
    ISSN 1471-0072
    DOI 10.1038/s41580-020-00289-8
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  2. Article ; Online: Features and mechanisms of canonical and noncanonical genomic imprinting.

    Hanna, Courtney W / Kelsey, Gavin

    Genes & development

    2021  Volume 35, Issue 11-12, Page(s) 821–834

    Abstract: Genomic imprinting is the monoallelic expression of a gene based on parent of origin and is a consequence of differential epigenetic marking between the male and female germlines. Canonically, genomic imprinting is mediated by allelic DNA methylation. ... ...

    Abstract Genomic imprinting is the monoallelic expression of a gene based on parent of origin and is a consequence of differential epigenetic marking between the male and female germlines. Canonically, genomic imprinting is mediated by allelic DNA methylation. However, recently it has been shown that maternal H3K27me3 can result in DNA methylation-independent imprinting, termed "noncanonical imprinting." In this review, we compare and contrast what is currently known about the underlying mechanisms, the role of endogenous retroviral elements, and the conservation of canonical and noncanonical genomic imprinting.
    MeSH term(s) DNA Methylation ; Epigenomics ; Genomic Imprinting/physiology ; Humans ; Retroelements/genetics
    Chemical Substances Retroelements
    Language English
    Publishing date 2021-06-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 806684-x
    ISSN 1549-5477 ; 0890-9369
    ISSN (online) 1549-5477
    ISSN 0890-9369
    DOI 10.1101/gad.348422.121
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  3. Article ; Online: Leptin signalling regulates transcriptional differences in granulosa cells from genetically obese mice but not the activation of NLRP3 inflammasome.

    Adamowski, Marek / Sharma, Yashaswi / Molcan, Tomasz / Wołodko, Karolina / Kelsey, Gavin / Galvão, António M

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 8070

    Abstract: Obesity is associated with increased ovarian inflammation and the establishment of leptin resistance. We presently investigated the role of impaired leptin signalling on transcriptional regulation in granulosa cells (GCs) collected from genetically obese ...

    Abstract Obesity is associated with increased ovarian inflammation and the establishment of leptin resistance. We presently investigated the role of impaired leptin signalling on transcriptional regulation in granulosa cells (GCs) collected from genetically obese mice. Furthermore, we characterised the association between ovarian leptin signalling, the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and macrophage infiltration in obese mice. After phenotype characterisation, ovaries were collected from distinct group of animals for protein and mRNA expression analysis: (i) mice subjected to a diet-induced obesity (DIO) protocol, where one group was fed a high-fat diet (HFD) and another a standard chow diet (CD) for durations of 4 or 16 weeks; (ii) mice genetically deficient in the long isoform of the leptin receptor (ObRb; db/db); (iii) mice genetically deficient in leptin (ob/ob); and (iv) mice rendered pharmacologically hyperleptinemic (LEPT). Next, GCs from antral follicles isolated from db/db and ob/ob mice were subjected to transcriptome analysis. Transcriptional analysis revealed opposing profiles in genes associated with steroidogenesis and prostaglandin action between the genetic models, despite the similarities in body weight. Furthermore, we observed no changes in the mRNA and protein levels of NLRP3 inflammasome components in the ovaries of db/db mice or in markers of M1 and M2 macrophage infiltration. This contrasted with the downregulation of NLRP3 inflammasome components and M1 markers in ob/ob and 16-wk HFD-fed mice. We concluded that leptin signalling regulates NLRP3 inflammasome activation and the expression of M1 markers in the ovaries of obese mice in an ObRb-dependent and ObRb-independent manner. Furthermore, we found no changes in the expression of leptin signalling and NLRP3 inflammasome genes in GCs from db/db and ob/ob mice, which was associated with no effects on macrophage infiltration genes, despite the dysregulation of genes associated with steroidogenesis in homozygous obese db/db. Our results suggest that: (i) the crosstalk between leptin signalling, NLRP3 inflammasome and macrophage infiltration takes place in ovarian components other than the GC compartment; and (ii) transcriptional changes in GCs from homozygous obese ob/ob mice suggest structural rearrangement and organisation, whereas in db/db mice the impairment in steroidogenesis and secretory activity.
    MeSH term(s) Animals ; Female ; Mice ; Granulosa Cells/metabolism ; Inflammasomes/genetics ; Leptin/metabolism ; Mice, Obese ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; NLR Proteins ; Obesity/metabolism ; Receptors, Leptin/genetics ; RNA, Messenger
    Chemical Substances Inflammasomes ; Lep protein, mouse ; Leptin ; NLR Family, Pyrin Domain-Containing 3 Protein ; NLR Proteins ; Nlrp3 protein, mouse ; Receptors, Leptin ; RNA, Messenger
    Language English
    Publishing date 2024-04-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-58181-w
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  4. Article ; Online: Keeping methylation at bay.

    Kelsey, Gavin

    Nature genetics

    2015  Volume 47, Issue 5, Page(s) 427–428

    Abstract: A hallmark of CpG islands is their unmethylated state, and determining how DNA methylation can invade these elements is therefore important for understanding developmental gene regulation and disease. A new study shows that FBXL10, a protein commonly ... ...

    Abstract A hallmark of CpG islands is their unmethylated state, and determining how DNA methylation can invade these elements is therefore important for understanding developmental gene regulation and disease. A new study shows that FBXL10, a protein commonly altered by mutation in leukemia, is part of a mechanism that blocks methylation of CpG islands.
    MeSH term(s) Animals ; DNA Methylation ; F-Box Proteins/physiology ; Jumonji Domain-Containing Histone Demethylases/physiology ; Male ; Polycomb-Group Proteins/metabolism ; Promoter Regions, Genetic
    Chemical Substances F-Box Proteins ; Polycomb-Group Proteins ; Jumonji Domain-Containing Histone Demethylases (EC 1.14.11.-)
    Language English
    Publishing date 2015-04-27
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/ng.3290
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  5. Article ; Online: The enigma of DNA methylation in the mammalian oocyte.

    Demond, Hannah / Kelsey, Gavin

    F1000Research

    2020  Volume 9

    Abstract: The mammalian genome experiences profound setting and resetting of epigenetic patterns during the life-course. This is understood best for DNA methylation: the specification of germ cells, gametogenesis, and early embryo development are characterised by ... ...

    Abstract The mammalian genome experiences profound setting and resetting of epigenetic patterns during the life-course. This is understood best for DNA methylation: the specification of germ cells, gametogenesis, and early embryo development are characterised by phases of widespread erasure and rewriting of methylation. While mitigating against intergenerational transmission of epigenetic information, these processes must also ensure correct genomic imprinting that depends on faithful and long-term memory of gamete-derived methylation states in the next generation. This underscores the importance of understanding the mechanisms of methylation programming in the germline.
    MeSH term(s) Animals ; Chromatin ; DNA Methylation ; Genomic Imprinting ; Germ Cells ; Mammals ; Oocytes
    Chemical Substances Chromatin
    Language English
    Publishing date 2020-02-25
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2699932-8
    ISSN 2046-1402 ; 2046-1402
    ISSN (online) 2046-1402
    ISSN 2046-1402
    DOI 10.12688/f1000research.21513.1
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  6. Article ; Online: Profiling DNA Methylation Genome-Wide in Single Cells.

    Galvão, António / Kelsey, Gavin

    Methods in molecular biology (Clifton, N.J.)

    2020  Volume 2214, Page(s) 221–240

    Abstract: Single-cell bisulfite sequencing (scBS-seq) enables profiling of DNA methylation at single-nucleotide resolution and across all genomic features. It can explore methylation differences between cells in mixed cell populations and profile methylation in ... ...

    Abstract Single-cell bisulfite sequencing (scBS-seq) enables profiling of DNA methylation at single-nucleotide resolution and across all genomic features. It can explore methylation differences between cells in mixed cell populations and profile methylation in very rare cell types, such as mammalian oocytes and cells from early embryos. Here, we outline the scBS-seq protocol in a 96-well plate format applicable to studies of moderate throughput.
    MeSH term(s) Animals ; DNA Methylation ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Sequence Analysis, DNA/methods ; Single-Cell Analysis/methods ; Sulfites/chemistry ; Whole Genome Sequencing/methods
    Chemical Substances Sulfites ; hydrogen sulfite (OJ9787WBLU)
    Language English
    Publishing date 2020-09-17
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-0958-3_15
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  7. Article ; Online: The role and mechanisms of DNA methylation in the oocyte.

    Sendžikaitė, Gintarė / Kelsey, Gavin

    Essays in biochemistry

    2019  Volume 63, Issue 6, Page(s) 691–705

    Abstract: Epigenetic information in the mammalian oocyte has the potential to be transmitted to the next generation and influence gene expression; this occurs naturally in the case of imprinted genes. Therefore, it is important to understand how epigenetic ... ...

    Abstract Epigenetic information in the mammalian oocyte has the potential to be transmitted to the next generation and influence gene expression; this occurs naturally in the case of imprinted genes. Therefore, it is important to understand how epigenetic information is patterned during oocyte development and growth. Here, we review the current state of knowledge of de novo DNA methylation mechanisms in the oocyte: how a distinctive gene-body methylation pattern is created, and the extent to which the DNA methylation machinery reads chromatin states. Recent epigenomic studies building on advances in ultra-low input chromatin profiling methods, coupled with genetic studies, have started to allow a detailed interrogation of the interplay between DNA methylation establishment and chromatin states; however, a full mechanistic description awaits.
    MeSH term(s) Animals ; Chromatin/metabolism ; DNA/metabolism ; DNA (Cytosine-5-)-Methyltransferases/physiology ; DNA Methylation/physiology ; Epigenesis, Genetic/physiology ; Humans ; Oocytes/metabolism
    Chemical Substances Chromatin ; DNA (9007-49-2) ; DNA (Cytosine-5-)-Methyltransferases (EC 2.1.1.37)
    Language English
    Publishing date 2019-11-28
    Publishing country England
    Document type Journal Article ; Review
    ISSN 1744-1358 ; 0071-1365
    ISSN (online) 1744-1358
    ISSN 0071-1365
    DOI 10.1042/EBC20190043
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  8. Article ; Online: Single-cell profiling reveals transcriptome dynamics during bovine oocyte growth.

    Latorraca, Lais Barbosa / Galvão, António / Rabaglino, Maria Belen / D'Augero, Julieta Maria / Kelsey, Gavin / Fair, Trudee

    BMC genomics

    2024  Volume 25, Issue 1, Page(s) 335

    Abstract: Background: Mammalian follicle development is characterized by extensive changes in morphology, endocrine responsiveness, and function, providing the optimum environment for oocyte growth, development, and resumption of meiosis. In cattle, the first ... ...

    Abstract Background: Mammalian follicle development is characterized by extensive changes in morphology, endocrine responsiveness, and function, providing the optimum environment for oocyte growth, development, and resumption of meiosis. In cattle, the first signs of transcription activation in the oocyte are observed in the secondary follicle, later than during mouse and human oogenesis. While many studies have generated extensive datasets characterizing gene expression in bovine oocytes, they are mostly limited to the analysis of fully grown and matured oocytes. The aim of the present study was to apply single-cell RNA sequencing to interrogate the transcriptome of the growing bovine oocyte from the secondary follicle stage through to the mid-antral follicle stage.
    Results: Single-cell RNA-seq libraries were generated from oocytes of known diameters (< 60 to > 120 μm), and datasets were binned into non-overlapping size groups for downstream analysis. Combining the results of weighted gene co-expression network and Trendy analyses, and differently expressed genes (DEGs) between size groups, we identified a decrease in oxidative phosphorylation and an increase in maternal -genes and transcription regulators across the bovine oocyte growth phase. In addition, around 5,000 genes did not change in expression, revealing a cohort of stable genes. An interesting switch in gene expression profile was noted in oocytes greater than 100 μm in diameter, when the expression of genes related to cytoplasmic activities was replaced by genes related to nuclear activities (e.g., chromosome segregation). The highest number of DEGs were detected in the comparison of oocytes 100-109 versus 110-119 μm in diameter, revealing a profound change in the molecular profile of oocytes at the end of their growth phase.
    Conclusions: The current study provides a unique dataset of the key genes and pathways characteristic of each stage of oocyte development, contributing an important resource for a greater understanding of bovine oogenesis.
    MeSH term(s) Female ; Cattle ; Animals ; Humans ; Mice ; Transcriptome ; Oogenesis/genetics ; Oocytes/metabolism ; Ovarian Follicle/metabolism ; Cell Proliferation ; Mammals/genetics
    Language English
    Publishing date 2024-04-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041499-7
    ISSN 1471-2164 ; 1471-2164
    ISSN (online) 1471-2164
    ISSN 1471-2164
    DOI 10.1186/s12864-024-10234-0
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  9. Article ; Online: DNA methylation: a new twist in the tail.

    Kelsey, Gavin

    Cell research

    2011  Volume 21, Issue 8, Page(s) 1155–1156

    MeSH term(s) Animals ; Chromatin/metabolism ; CpG Islands ; DNA (Cytosine-5-)-Methyltransferases/chemistry ; DNA (Cytosine-5-)-Methyltransferases/metabolism ; DNA Methylation ; DNA Methyltransferase 3A ; Histones/metabolism ; Mice ; Protein Structure, Tertiary ; DNA Methyltransferase 3B
    Chemical Substances Chromatin ; Histones ; Dnmt3l protein, mouse (EC 2.1.1.-) ; DNA (Cytosine-5-)-Methyltransferases (EC 2.1.1.37) ; DNA Methyltransferase 3A (EC 2.1.1.37)
    Language English
    Publishing date 2011-07-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 1319303-x
    ISSN 1748-7838 ; 1001-0602
    ISSN (online) 1748-7838
    ISSN 1001-0602
    DOI 10.1038/cr.2011.110
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  10. Article ; Online: A web of imprinting in stem cells.

    Kelsey, Gavin

    Cell stem cell

    2011  Volume 9, Issue 3, Page(s) 177–178

    Abstract: Imprinted genes are the prototypical epigenetically regulated genes. On the basis of findings in adult lung stem cells, Zacharek et al. (2011) suggest in this issue of Cell Stem Cell that epigenetic silencing of imprinted genes is a common requirement ... ...

    Abstract Imprinted genes are the prototypical epigenetically regulated genes. On the basis of findings in adult lung stem cells, Zacharek et al. (2011) suggest in this issue of Cell Stem Cell that epigenetic silencing of imprinted genes is a common requirement for maintaining self-renewal in adult stem cell populations.
    MeSH term(s) Adult Stem Cells/metabolism ; Animals ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Gene Expression Regulation, Developmental ; Nuclear Proteins/metabolism ; Polycomb Repressive Complex 1 ; Proto-Oncogene Proteins/metabolism ; Repressor Proteins/metabolism ; S-Phase Kinase-Associated Proteins/metabolism
    Chemical Substances Bmi1 protein, mouse ; Cyclin-Dependent Kinase Inhibitor p16 ; Nuclear Proteins ; Proto-Oncogene Proteins ; Repressor Proteins ; S-Phase Kinase-Associated Proteins ; Polycomb Repressive Complex 1 (EC 2.3.2.27)
    Language English
    Publishing date 2011-08-09
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2011.08.008
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