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  1. Book ; Online: Follicular Helper T Cells in Immunity and Autoimmunity

    Fousteri, Georgia / Salek-Ardakani, Shahram / Pia Cicalese, Maria / Pia Cicalese, Maria

    2020  

    Keywords Medicine ; Immunology ; follicular helper T cells ; follicular regulatory T cells ; autoimmunity ; primary immunodeficiency ; immunity ; cancer ; infection ; transplantation
    Size 1 electronic resource (349 pages)
    Publisher Frontiers Media SA
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT021229977
    ISBN 9782889638475 ; 2889638472
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article ; Online: Enhanced frequency of transcription pre-initiation complexes assembly after exposure to UV irradiation results in increased repair activity and reduced probabilities for mutagenesis.

    Liakos, Anastasios / Synacheri, Anna-Chloe / Konstantopoulos, Dimitris / Stefos, Georgios C / Lavigne, Matthieu D / Fousteri, Maria

    Nucleic acids research

    2023  Volume 51, Issue 16, Page(s) 8575–8586

    Abstract: In addition to being essential for gene expression, transcription is crucial for the maintenance of genome integrity. Here, we undertook a systematic approach, to monitor the assembly kinetics of the pre-initiating RNA Polymerase (Pol) II at promoters at ...

    Abstract In addition to being essential for gene expression, transcription is crucial for the maintenance of genome integrity. Here, we undertook a systematic approach, to monitor the assembly kinetics of the pre-initiating RNA Polymerase (Pol) II at promoters at steady state and different stages during recovery from UV irradiation-stress, when pre-initiation and initiation steps have been suggested to be transiently shut down. Taking advantage of the reversible dissociation of pre-initiating Pol II after high salt treatment, we found that de novo recruitment of the available Pol II molecules at active promoters not only persists upon UV at all times tested but occurs significantly faster in the early phase of recovery (2 h) than in unexposed human fibroblasts at the majority of active genes. Our method unveiled groups of genes with significantly different pre-initiation complex (PIC) assembly dynamics after UV that present distinct rates of UV-related mutational signatures in melanoma tumours, providing functional relevance to the importance of keeping transcription initiation active during UV recovery. Our findings uncover novel mechanistic insights further detailing the multilayered transcriptional response to genotoxic stress and link PIC assembly dynamics after exposure to genotoxins with cancer mutational landscapes.
    MeSH term(s) Humans ; DNA Damage ; Mutagenesis ; Promoter Regions, Genetic ; RNA Polymerase II/genetics ; RNA Polymerase II/metabolism ; Transcription, Genetic ; Ultraviolet Rays ; Transcription Initiation, Genetic ; Fibroblasts/metabolism ; DNA Repair
    Chemical Substances RNA Polymerase II (EC 2.7.7.-)
    Language English
    Publishing date 2023-07-20
    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/gkad593
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Editorial: Follicular Helper T Cells in Immunity and Autoimmunity.

    Cicalese, Maria Pia / Salek-Ardakani, Shahram / Fousteri, Georgia

    Frontiers in immunology

    2020  Volume 11, Page(s) 1042

    MeSH term(s) Animals ; Autoimmunity ; Germinal Center/immunology ; Humans ; Immunity ; T Follicular Helper Cells/immunology ; T-Lymphocytes, Helper-Inducer/immunology
    Language English
    Publishing date 2020-05-29
    Publishing country Switzerland
    Document type Editorial ; Introductory Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.01042
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Histone H2Bub dynamics in the 5' region of active genes are tightly linked to the UV-induced transcriptional response.

    Fanourgakis, Smaragda / Synacheri, Anna-Chloe / Lavigne, Matthieu D / Konstantopoulos, Dimitris / Fousteri, Maria

    Computational and structural biotechnology journal

    2022  Volume 21, Page(s) 614–629

    Abstract: The timing and location of writing and erasing of histone modifications determine gene expression programs and are tightly controlled processes. One such modification is the monoubiquitination of histone H2B (H2Bub), whose precise level during ... ...

    Abstract The timing and location of writing and erasing of histone modifications determine gene expression programs and are tightly controlled processes. One such modification is the monoubiquitination of histone H2B (H2Bub), whose precise level during transcription elongation is dynamically regulated by the synergistic action of RNF20/40 ubiquitin-ligase and the de-ubiquitinase (DUB) of the ATXN7L3-containing DUB modules. Here, we characterize the dynamics of H2Bub in transcription and explore its role in perspective with the recently updated model of UV damage-induced transcription reorganization. Employing integrative analysis of genome-wide high-throughput approaches, transcription inhibitors and ATXN7L3-DUB knockdown cells, we find that H2Bub levels and patterns depend on intron-exon architecture both in steady state and upon UV. Importantly, our analysis reveals a widespread redistribution of this histone mark, rather than a uniform loss as previously suggested, which closely mirrors the post-UV dynamics of elongating RNA Polymerase II (RNAPII) at transcribed loci. The observed effects are due to a direct inter-dependence on RNAPII local concentration and speed, and we show that deficient ATXN7L3-mediated DUB activity leads to increased elongation rates in both non-irradiated and irradiated conditions. Our data and the implementation of a high-resolution computational framework reveal that the H2Bub pattern follows that of RNAPII, both in the ATXNL3 knockdown and in response to UV guaranteeing faithful elongation speed, especially in the context of the transcription-driven DNA damage response.
    Language English
    Publishing date 2022-12-13
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2694435-2
    ISSN 2001-0370
    ISSN 2001-0370
    DOI 10.1016/j.csbj.2022.12.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Decoding of translation-regulating entities reveals heterogeneous translation deficiency patterns in cellular senescence.

    Papaspyropoulos, Angelos / Hazapis, Orsalia / Altulea, Abdullah / Polyzou, Aikaterini / Verginis, Panayotis / Evangelou, Konstantinos / Fousteri, Maria / Papantonis, Argyris / Demaria, Marco / Gorgoulis, Vassilis

    Aging cell

    2023  Volume 22, Issue 9, Page(s) e13893

    Abstract: Cellular senescence constitutes a generally irreversible proliferation barrier, accompanied by macromolecular damage and metabolic rewiring. Several senescence types have been identified based on the initiating stimulus, such as replicative (RS), stress- ... ...

    Abstract Cellular senescence constitutes a generally irreversible proliferation barrier, accompanied by macromolecular damage and metabolic rewiring. Several senescence types have been identified based on the initiating stimulus, such as replicative (RS), stress-induced (SIS) and oncogene-induced senescence (OIS). These senescence subtypes are heterogeneous and often develop subset-specific phenotypes. Reduced protein synthesis is considered a senescence hallmark, but whether this trait pertains to various senescence subtypes and if distinct molecular mechanisms are involved remain largely unknown. Here, we analyze large published or experimentally produced RNA-seq and Ribo-seq datasets to determine whether major translation-regulating entities such as ribosome stalling, the presence of uORFs/dORFs and IRES elements may differentially contribute to translation deficiency in senescence subsets. We show that translation-regulating mechanisms may not be directly relevant to RS, however uORFs are significantly enriched in SIS. Interestingly, ribosome stalling, uORF/dORF patterns and IRES elements comprise predominant mechanisms upon OIS, strongly correlating with Notch pathway activation. Our study provides for the first time evidence that major translation dysregulation mechanisms/patterns occur during cellular senescence, but at different rates depending on the stimulus type. The degree at which those mechanisms accumulate directly correlates with translation deficiency levels. Our thorough analysis contributes to elucidating crucial and so far unknown differences in the translation machinery between senescence subsets.
    MeSH term(s) Cellular Senescence/genetics ; Ribosomes/genetics ; Ribosomes/metabolism ; Protein Biosynthesis
    Language English
    Publishing date 2023-08-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2113083-8
    ISSN 1474-9726 ; 1474-9718
    ISSN (online) 1474-9726
    ISSN 1474-9718
    DOI 10.1111/acel.13893
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A machine learning approach to predict response to immunotherapy in type 1 diabetes.

    Fousteri, Georgia / Rodrigues, Ely Montee / Giamporcaro, Gian Maria / Falcone, Marika

    Cellular & molecular immunology

    2020  Volume 18, Issue 3, Page(s) 515–517

    MeSH term(s) Diabetes Mellitus, Type 1/therapy ; Humans ; Immunotherapy ; Machine Learning
    Language English
    Publishing date 2020-12-14
    Publishing country China
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2435097-7
    ISSN 2042-0226 ; 1672-7681
    ISSN (online) 2042-0226
    ISSN 1672-7681
    DOI 10.1038/s41423-020-00594-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Retraction Notice to: Cockayne Syndrome A and B Proteins Differentially Regulate Recruitment of Chromatin Remodeling and Repair Factors to Stalled RNA Polymerase II In Vivo.

    Fousteri, Maria / Vermeulen, Wim / van Zeeland, Albert A / Mullenders, Leon H F

    Molecular cell

    2021  Volume 81, Issue 24, Page(s) 5112

    Language English
    Publishing date 2021-12-30
    Publishing country United States
    Document type Journal Article ; Retraction of Publication
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2021.11.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Retraction Notice to: Sealing of Chromosomal DNA Nicks during Nucleotide Excision Repair Requires XRCC1 and DNA Ligase IIIα in a Cell-Cycle-Specific Manner.

    Moser, Jill / Kool, Hanneke / Giakzidis, Ioannis / Caldecott, Keith / Mullenders, Leon H F / Fousteri, Maria I

    Molecular cell

    2021  Volume 81, Issue 24, Page(s) 5113

    Language English
    Publishing date 2021-12-30
    Publishing country United States
    Document type Journal Article ; Retraction of Publication
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2021.11.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Continuous transcription initiation guarantees robust repair of all transcribed genes and regulatory regions.

    Liakos, Anastasios / Konstantopoulos, Dimitris / Lavigne, Matthieu D / Fousteri, Maria

    Nature communications

    2020  Volume 11, Issue 1, Page(s) 916

    Abstract: Inhibition of transcription caused by DNA damage-impaired RNA polymerase II (Pol II) elongation conceals a local increase in de novo transcription, slowly progressing from Transcription Start Sites (TSSs) to gene ends. Although associated with ... ...

    Abstract Inhibition of transcription caused by DNA damage-impaired RNA polymerase II (Pol II) elongation conceals a local increase in de novo transcription, slowly progressing from Transcription Start Sites (TSSs) to gene ends. Although associated with accelerated repair of Pol II-encountered lesions and limited mutagenesis, it is still unclear how this mechanism is maintained during genotoxic stress-recovery. Here we uncover a widespread gain in chromatin accessibility and preservation of the active H3K27ac mark after UV-irradiation. The concomitant increase in Pol II escape from promoter-proximal pause (PPP) sites of most active genes, PROMPTs and enhancer RNAs favors unrestrained initiation, as evidenced by the synthesis of nascent RNAs including start RNAs. Accordingly, drug-inhibition of PPP-release replenishes levels of pre-initiating Pol II at TSSs after UV. Our data show that such continuous engagement of Pol II molecules ensures maximal transcription-driven repair throughout expressed genes and regulatory loci. Importantly, revealing this unanticipated regulatory layer of UV-response provides physiological relevant traction to the emerging concept that Pol II initiation rate is determined by pause-release dynamics.
    MeSH term(s) Chromatin/genetics ; Chromatin/metabolism ; DNA Damage ; DNA Repair ; Gene Expression Regulation ; Humans ; Promoter Regions, Genetic ; RNA/genetics ; RNA/metabolism ; RNA Polymerase II/genetics ; RNA Polymerase II/metabolism ; Regulatory Sequences, Nucleic Acid ; Transcription Initiation Site ; Transcription, Genetic
    Chemical Substances Chromatin ; RNA (63231-63-0) ; RNA Polymerase II (EC 2.7.7.-)
    Language English
    Publishing date 2020-02-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-14566-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: aniFOUND: analysing the associated proteome and genomic landscape of the repaired nascent non-replicative chromatin.

    Stefos, Georgios C / Szantai, Eszter / Konstantopoulos, Dimitris / Samiotaki, Martina / Fousteri, Maria

    Nucleic acids research

    2021  Volume 49, Issue 11, Page(s) e64

    Abstract: Specific capture of chromatin fractions with distinct and well-defined features has emerged as both challenging and a key strategy towards a comprehensive understanding of genome biology. In this context, we developed aniFOUND (accelerated native ... ...

    Abstract Specific capture of chromatin fractions with distinct and well-defined features has emerged as both challenging and a key strategy towards a comprehensive understanding of genome biology. In this context, we developed aniFOUND (accelerated native isolation of factors on unscheduled nascent DNA), an antibody-free method, which can label, capture, map and characterise nascent chromatin fragments that are synthesized in response to specific cues outside S-phase. We used the 'unscheduled' DNA synthesis (UDS) that takes place during the repair of UV-induced DNA lesions and coupled the captured chromatin to high-throughput analytical technologies. By mass-spectrometry we identified several factors with no previously known role in UVC-DNA damage response (DDR) as well as known DDR proteins. We experimentally validated the repair-dependent recruitment of the chromatin remodeller RSF1 and the cohesin-loader NIPBL at sites of UVC-induced photolesions. Developing aniFOUND-seq, a protocol for mapping UDS activity with high resolution, allowed us to monitor the landscape of UVC repair-synthesis events genome wide. We further resolved repair efficacy of the rather unexplored repeated genome, in particular rDNA and telomeres. In summary, aniFOUND delineates the proteome composition and genomic landscape of chromatin loci with specific features by integrating state-of-the-art 'omics' technologies to promote a comprehensive view of their function.
    MeSH term(s) Cell Cycle Proteins/metabolism ; Cell Line ; Chromatin/metabolism ; DNA/biosynthesis ; DNA/radiation effects ; DNA Repair ; Genomics/methods ; High-Throughput Nucleotide Sequencing ; Humans ; Mass Spectrometry ; Nuclear Proteins/metabolism ; Proteome ; Proteomics/methods ; Repetitive Sequences, Nucleic Acid ; Trans-Activators/metabolism ; Ultraviolet Rays
    Chemical Substances Cell Cycle Proteins ; Chromatin ; NIPBL protein, human ; Nuclear Proteins ; Proteome ; RSF1 protein, human ; Trans-Activators ; DNA (9007-49-2)
    Language English
    Publishing date 2021-03-05
    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/gkab144
    Database MEDical Literature Analysis and Retrieval System OnLINE

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