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  1. Article ; Online: Direct recruitment of Mis18 to interphase spindle pole bodies promotes CENP-A chromatin assembly.

    London, Nitobe / Medina-Pritchard, Bethan / Spanos, Christos / Rappsilber, Juri / Jeyaprakash, A Arockia / Allshire, Robin C

    Current biology : CB

    2023  Volume 33, Issue 19, Page(s) 4187–4201.e6

    Abstract: CENP-A chromatin specifies mammalian centromere identity, and its chaperone HJURP replenishes CENP-A when recruited by the Mis18 complex (Mis18C) via M18BP1/KNL2 to CENP-C at kinetochores during interphase. However, the Mis18C recruitment mechanism ... ...

    Abstract CENP-A chromatin specifies mammalian centromere identity, and its chaperone HJURP replenishes CENP-A when recruited by the Mis18 complex (Mis18C) via M18BP1/KNL2 to CENP-C at kinetochores during interphase. However, the Mis18C recruitment mechanism remains unresolved in species lacking M18BP1, such as fission yeast. Fission yeast centromeres cluster at G2 spindle pole bodies (SPBs) when CENP-A
    MeSH term(s) Carrier Proteins/genetics ; Centromere/metabolism ; Centromere Protein A/metabolism ; Chromatin/metabolism ; Chromatin Assembly and Disassembly ; Chromosomal Proteins, Non-Histone/metabolism ; Interphase ; Schizosaccharomyces/genetics ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/genetics ; Schizosaccharomyces pombe Proteins/metabolism ; Spindle Pole Bodies/metabolism
    Chemical Substances Carrier Proteins ; Centromere Protein A ; Chromatin ; Chromosomal Proteins, Non-Histone ; Cnp1 protein, S pombe ; Mis18 protein, S pombe ; Schizosaccharomyces pombe Proteins
    Language English
    Publishing date 2023-09-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2023.08.063
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Establishment of centromere identity is dependent on nuclear spatial organization.

    Wu, Weifang / McHugh, Toni / Kelly, David A / Pidoux, Alison L / Allshire, Robin C

    Current biology : CB

    2022  Volume 32, Issue 14, Page(s) 3121–3136.e6

    Abstract: The establishment of centromere-specific CENP-A chromatin is influenced by epigenetic and genetic processes. Central domain sequences from fission yeast centromeres are preferred substrates for CENP- ... ...

    Abstract The establishment of centromere-specific CENP-A chromatin is influenced by epigenetic and genetic processes. Central domain sequences from fission yeast centromeres are preferred substrates for CENP-A
    MeSH term(s) Centromere/metabolism ; Centromere Protein A/metabolism ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; DNA/genetics ; Heterochromatin/genetics ; Heterochromatin/metabolism ; Histones/metabolism ; Schizosaccharomyces/genetics ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/genetics ; Schizosaccharomyces pombe Proteins/metabolism
    Chemical Substances Centromere Protein A ; Chromosomal Proteins, Non-Histone ; Cnp1 protein, S pombe ; Heterochromatin ; Histones ; Schizosaccharomyces pombe Proteins ; DNA (9007-49-2)
    Language English
    Publishing date 2022-07-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2022.06.048
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Ten principles of heterochromatin formation and function.

    Allshire, Robin C / Madhani, Hiten D

    Nature reviews. Molecular cell biology

    2017  Volume 19, Issue 4, Page(s) 229–244

    Abstract: Heterochromatin is a key architectural feature of eukaryotic chromosomes, which endows particular genomic domains with specific functional properties. The capacity of heterochromatin to restrain the activity of mobile elements, isolate DNA repair in ... ...

    Abstract Heterochromatin is a key architectural feature of eukaryotic chromosomes, which endows particular genomic domains with specific functional properties. The capacity of heterochromatin to restrain the activity of mobile elements, isolate DNA repair in repetitive regions and ensure accurate chromosome segregation is crucial for maintaining genomic stability. Nucleosomes at heterochromatin regions display histone post-translational modifications that contribute to developmental regulation by restricting lineage-specific gene expression. The mechanisms of heterochromatin establishment and of heterochromatin maintenance are separable and involve the ability of sequence-specific factors bound to nascent transcripts to recruit chromatin-modifying enzymes. Heterochromatin can spread along the chromatin from nucleation sites. The propensity of heterochromatin to promote its own spreading and inheritance is counteracted by inhibitory factors. Because of its importance for chromosome function, heterochromatin has key roles in the pathogenesis of various human diseases. In this Review, we discuss conserved principles of heterochromatin formation and function using selected examples from studies of a range of eukaryotes, from yeast to human, with an emphasis on insights obtained from unicellular model organisms.
    MeSH term(s) Aging, Premature/genetics ; Animals ; Cell Differentiation/genetics ; Chromatin Assembly and Disassembly/genetics ; Chromatin Assembly and Disassembly/physiology ; DNA Methylation ; DNA Repair ; Epigenesis, Genetic ; Gene Silencing ; Heterochromatin/genetics ; Heterochromatin/metabolism ; Humans ; Models, Biological ; Obesity/genetics ; RNA, Fungal/genetics ; RNA, Fungal/metabolism ; RNA, Untranslated/genetics ; RNA, Untranslated/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Schizosaccharomyces/genetics ; Schizosaccharomyces/metabolism ; Virus Latency/genetics
    Chemical Substances Heterochromatin ; RNA, Fungal ; RNA, Untranslated
    Language English
    Publishing date 2017-12-13
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2031313-5
    ISSN 1471-0080 ; 1471-0072
    ISSN (online) 1471-0080
    ISSN 1471-0072
    DOI 10.1038/nrm.2017.119
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Transcription-coupled changes to chromatin underpin gene silencing by transcriptional interference.

    Ard, Ryan / Allshire, Robin C

    Nucleic acids research

    2016  Volume 44, Issue 22, Page(s) 10619–10630

    Abstract: Long non-coding RNA (lncRNA) transcription into a downstream promoter frequently results in transcriptional interference. However, the mechanism of this repression is not fully understood. We recently showed that drug tolerance in fission yeast ... ...

    Abstract Long non-coding RNA (lncRNA) transcription into a downstream promoter frequently results in transcriptional interference. However, the mechanism of this repression is not fully understood. We recently showed that drug tolerance in fission yeast Schizosaccharomyces pombe is controlled by lncRNA transcription upstream of the tgp1
    MeSH term(s) Acid Phosphatase/genetics ; Acid Phosphatase/metabolism ; Chromatin/genetics ; Chromatin/metabolism ; Gene Expression Regulation, Fungal ; Gene Silencing ; Genes, Fungal ; Histone-Lysine N-Methyltransferase/genetics ; Histone-Lysine N-Methyltransferase/metabolism ; Histones ; Methylation ; Promoter Regions, Genetic ; Protein Processing, Post-Translational ; Schizosaccharomyces/genetics ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/genetics ; Schizosaccharomyces pombe Proteins/metabolism ; Transcription, Genetic
    Chemical Substances Chromatin ; Histones ; Schizosaccharomyces pombe Proteins ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43) ; Set2 protein, S pombe (EC 2.1.1.43) ; Acid Phosphatase (EC 3.1.3.2) ; acid phosphatase Pho1, S pombe (EC 3.1.3.2)
    Language English
    Publishing date 2016-12-15
    Publishing country England
    Document type Journal Article
    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/gkw801
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Epigenetic Regulation of Chromatin States in Schizosaccharomyces pombe.

    Allshire, Robin C / Ekwall, Karl

    Cold Spring Harbor perspectives in biology

    2015  Volume 7, Issue 7, Page(s) a018770

    Abstract: This article discusses the advances made in epigenetic research using the model organism fission yeast Schizosaccharomyces pombe. S. pombe has been used for epigenetic research since the discovery of position effect variegation (PEV). This is a ... ...

    Abstract This article discusses the advances made in epigenetic research using the model organism fission yeast Schizosaccharomyces pombe. S. pombe has been used for epigenetic research since the discovery of position effect variegation (PEV). This is a phenomenon in which a transgene inserted within heterochromatin is variably expressed, but can be stably inherited in subsequent cell generations. PEV occurs at centromeres, telomeres, ribosomal DNA (rDNA) loci, and mating-type regions of S. pombe chromosomes. Heterochromatin assembly in these regions requires enzymes that modify histones and the RNA interference (RNAi) machinery. One of the key histone-modifying enzymes is the lysine methyltransferase Clr4, which methylates histone H3 on lysine 9 (H3K9), a classic hallmark of heterochromatin. The kinetochore is assembled on specialized chromatin in which histone H3 is replaced by the variant CENP-A. Studies in fission yeast have contributed to our understanding of the establishment and maintenance of CENP-A chromatin and the epigenetic activation and inactivation of centromeres.
    MeSH term(s) Autoantigens ; Centromere Protein A ; Chromatin/metabolism ; Chromatin Assembly and Disassembly ; Chromosomal Proteins, Non-Histone ; Epigenesis, Genetic ; Heterochromatin/metabolism ; Histones/metabolism ; Models, Genetic ; Nucleosomes/metabolism ; RNA Interference ; RNA Polymerase II/physiology ; Schizosaccharomyces/genetics ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/metabolism
    Chemical Substances Autoantigens ; Centromere Protein A ; Chromatin ; Chromosomal Proteins, Non-Histone ; Heterochromatin ; Histones ; Nucleosomes ; Schizosaccharomyces pombe Proteins ; RNA Polymerase II (EC 2.7.7.-)
    Language English
    Publishing date 2015-07-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ISSN 1943-0264
    ISSN (online) 1943-0264
    DOI 10.1101/cshperspect.a018770
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The SPARC complex defines RNAPII promoters in

    Staneva, Desislava P / Bresson, Stefan / Auchynnikava, Tatsiana / Spanos, Christos / Rappsilber, Juri / Jeyaprakash, A Arockia / Tollervey, David / Matthews, Keith R / Allshire, Robin C

    eLife

    2022  Volume 11

    Abstract: Kinetoplastids are a highly divergent lineage of eukaryotes with unusual mechanisms for regulating gene expression. We previously surveyed 65 putative chromatin factors in the ... ...

    Abstract Kinetoplastids are a highly divergent lineage of eukaryotes with unusual mechanisms for regulating gene expression. We previously surveyed 65 putative chromatin factors in the kinetoplastid
    MeSH term(s) Chromatin/metabolism ; Heterochromatin/metabolism ; Histone Methyltransferases/genetics ; RNA Polymerase II/metabolism ; RNA, Messenger/metabolism ; Transcription, Genetic ; Trypanosoma brucei brucei/genetics ; Trypanosoma brucei brucei/metabolism ; Variant Surface Glycoproteins, Trypanosoma/genetics
    Chemical Substances Chromatin ; Heterochromatin ; RNA, Messenger ; Variant Surface Glycoproteins, Trypanosoma ; Histone Methyltransferases (EC 2.1.1.-) ; RNA Polymerase II (EC 2.7.7.-)
    Language English
    Publishing date 2022-09-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.83135
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  7. Article ; Online: Emerging Properties and Functional Consequences of Noncoding Transcription.

    Ard, Ryan / Allshire, Robin C / Marquardt, Sebastian

    Genetics

    2017  Volume 207, Issue 2, Page(s) 357–367

    Abstract: Eukaryotic genomes are rich in transcription units encoding "long noncoding RNAs" (lncRNAs). The purpose of all this transcription is unclear since most lncRNAs are quickly targeted for destruction during synthesis or shortly thereafter. As debates ... ...

    Abstract Eukaryotic genomes are rich in transcription units encoding "long noncoding RNAs" (lncRNAs). The purpose of all this transcription is unclear since most lncRNAs are quickly targeted for destruction during synthesis or shortly thereafter. As debates continue over the functional significance of many specific lncRNAs, support grows for the notion that the act of transcription rather than the RNA product itself is functionally important in many cases. Indeed, this alternative mechanism might better explain how low-abundance lncRNAs transcribed from noncoding DNA function in organisms. Here, we highlight some of the recently emerging features that distinguish coding from noncoding transcription and discuss how these differences might have important implications for the functional consequences of noncoding transcription.
    MeSH term(s) Animals ; Chromatin/genetics ; Chromatin/metabolism ; Humans ; RNA Polymerase II/metabolism ; RNA Stability ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Transcription, Genetic
    Chemical Substances Chromatin ; RNA, Long Noncoding ; RNA Polymerase II (EC 2.7.7.-)
    Language English
    Publishing date 2017-10-05
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2167-2
    ISSN 1943-2631 ; 0016-6731
    ISSN (online) 1943-2631
    ISSN 0016-6731
    DOI 10.1534/genetics.117.300095
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  8. Article ; Online: A systematic analysis of

    Staneva, Desislava P / Carloni, Roberta / Auchynnikava, Tatsiana / Tong, Pin / Rappsilber, Juri / Jeyaprakash, A Arockia / Matthews, Keith R / Allshire, Robin C

    Genome research

    2021  Volume 31, Issue 11, Page(s) 2138–2154

    Abstract: Nucleosomes composed of histones are the fundamental units around which DNA is wrapped to form chromatin. Transcriptionally active euchromatin or repressive heterochromatin is regulated in part by the addition or removal of histone post-translational ... ...

    Abstract Nucleosomes composed of histones are the fundamental units around which DNA is wrapped to form chromatin. Transcriptionally active euchromatin or repressive heterochromatin is regulated in part by the addition or removal of histone post-translational modifications (PTMs) by "writer" and "eraser" enzymes, respectively. Nucleosomal PTMs are recognized by a variety of "reader" proteins that alter gene expression accordingly. The histone tails of the evolutionarily divergent eukaryotic parasite
    MeSH term(s) Chromatin/genetics ; Chromatin/metabolism ; Nucleosomes/metabolism ; Protein Interaction Maps ; Proteomics ; Trypanosoma brucei brucei/genetics ; Trypanosoma brucei brucei/metabolism
    Chemical Substances Chromatin ; Nucleosomes
    Language English
    Publishing date 2021-08-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1284872-4
    ISSN 1549-5469 ; 1088-9051 ; 1054-9803
    ISSN (online) 1549-5469
    ISSN 1088-9051 ; 1054-9803
    DOI 10.1101/gr.275368.121
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  9. Article ; Online: Anarchic centromeres: deciphering order from apparent chaos.

    Catania, Sandra / Allshire, Robin C

    Current opinion in cell biology

    2013  Volume 26, Page(s) 41–50

    Abstract: Specialised chromatin in which canonical histone H3 is replaced by CENP-A, an H3 related protein, is a signature of active centromeres and provides the foundation for kinetochore assembly. The location of centromeres is not fixed since centromeres can be ...

    Abstract Specialised chromatin in which canonical histone H3 is replaced by CENP-A, an H3 related protein, is a signature of active centromeres and provides the foundation for kinetochore assembly. The location of centromeres is not fixed since centromeres can be inactivated and new centromeres can arise at novel locations independently of specific DNA sequence elements. Therefore, the establishment and maintenance of CENP-A chromatin and kinetochores provide an exquisite example of genuine epigenetic regulation. The composition of CENP-A nucleosomes is contentious but several studies suggest that, like regular H3 particles, they are octamers. Recent analyses have provided insight into how CENP-A is recognised and propagated, identified roles for post-translational modifications and dissected how CENP-A recruits other centromere proteins to mediate kinetochore assembly.
    MeSH term(s) Animals ; Autoantigens/chemistry ; Autoantigens/metabolism ; Centromere/chemistry ; Centromere/metabolism ; Centromere Protein A ; Chromatin/chemistry ; Chromatin/metabolism ; Chromosomal Proteins, Non-Histone/chemistry ; Chromosomal Proteins, Non-Histone/metabolism ; Humans ; Nucleosomes/chemistry ; Nucleosomes/metabolism ; Protein Binding ; Protein Processing, Post-Translational
    Chemical Substances Autoantigens ; CENPA protein, human ; Centromere Protein A ; Chromatin ; Chromosomal Proteins, Non-Histone ; Nucleosomes
    Language English
    Publishing date 2013-10-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1026381-0
    ISSN 1879-0410 ; 0955-0674
    ISSN (online) 1879-0410
    ISSN 0955-0674
    DOI 10.1016/j.ceb.2013.09.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line.

    Zoch, Ansgar / Konieczny, Gabriela / Auchynnikava, Tania / Stallmeyer, Birgit / Rotte, Nadja / Heep, Madeleine / Berrens, Rebecca V / Schito, Martina / Kabayama, Yuka / Schöpp, Theresa / Kliesch, Sabine / Houston, Brendan / Nagirnaja, Liina / O'Bryan, Moira K / Aston, Kenneth I / Conrad, Donald F / Rappsilber, Juri / Allshire, Robin C / Cook, Atlanta G /
    Tüttelmann, Frank / O'Carroll, Dónal

    Molecular cell

    2024  Volume 84, Issue 6, Page(s) 1021–1035.e11

    Abstract: In the male mouse germ line, PIWI-interacting RNAs (piRNAs), bound by the PIWI protein MIWI2 (PIWIL4), guide DNA methylation of young active transposons through SPOCD1. However, the underlying mechanisms of SPOCD1-mediated piRNA-directed transposon ... ...

    Abstract In the male mouse germ line, PIWI-interacting RNAs (piRNAs), bound by the PIWI protein MIWI2 (PIWIL4), guide DNA methylation of young active transposons through SPOCD1. However, the underlying mechanisms of SPOCD1-mediated piRNA-directed transposon methylation and whether this pathway functions to protect the human germ line remain unknown. We identified loss-of-function variants in human SPOCD1 that cause defective transposon silencing and male infertility. Through the analysis of these pathogenic alleles, we discovered that the uncharacterized protein C19ORF84 interacts with SPOCD1. DNMT3C, the DNA methyltransferase responsible for transposon methylation, associates with SPOCD1 and C19ORF84 in fetal gonocytes. Furthermore, C19ORF84 is essential for piRNA-directed DNA methylation and male mouse fertility. Finally, C19ORF84 mediates the in vivo association of SPOCD1 with the de novo methylation machinery. In summary, we have discovered a conserved role for the human piRNA pathway in transposon silencing and C19ORF84, an uncharacterized protein essential for orchestrating piRNA-directed DNA methylation.
    MeSH term(s) Male ; Humans ; Animals ; Mice ; DNA Methylation ; Piwi-Interacting RNA ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Proteins/metabolism ; Germ Cells/metabolism ; Argonaute Proteins/genetics ; Argonaute Proteins/metabolism ; DNA Transposable Elements/genetics ; Mammals/metabolism
    Chemical Substances Piwi-Interacting RNA ; RNA, Small Interfering ; Proteins ; Argonaute Proteins ; DNA Transposable Elements ; PIWIL4 protein, mouse
    Language English
    Publishing date 2024-02-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2024.01.014
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