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  1. Article ; Online: Clonal hematopoiesis, inflammation, and cardiovascular disorders: a mitochondrial connection.

    Pileri, Francesco / Natoli, Gioacchino

    Trends in immunology

    2022  Volume 43, Issue 9, Page(s) 693–695

    Abstract: Mutations in two antagonistic regulators of DNA methylation, DNMT3A and TET2, are associated with clonal hematopoiesis and increased risk of cardiovascular disorders. Recently, Cobo et al. traced the mechanistic bases for such links to loss of ... ...

    Abstract Mutations in two antagonistic regulators of DNA methylation, DNMT3A and TET2, are associated with clonal hematopoiesis and increased risk of cardiovascular disorders. Recently, Cobo et al. traced the mechanistic bases for such links to loss of mitochondrial integrity, cytoplasmic dispersion of mitochondrial DNA, and the subsequent activation of interferon-stimulated genes (ISGs) in macrophages.
    MeSH term(s) Cardiovascular Diseases ; Clonal Hematopoiesis ; Hematopoiesis ; Humans ; Inflammation ; Mutation
    Language English
    Publishing date 2022-08-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2036831-8
    ISSN 1471-4981 ; 1471-4906
    ISSN (online) 1471-4981
    ISSN 1471-4906
    DOI 10.1016/j.it.2022.07.009
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  2. Article ; Online: From the Beauty of Genomic Landscapes to the Strength of Transcriptional Mechanisms.

    Natoli, Gioacchino

    Cell

    2016  Volume 165, Issue 1, Page(s) 18–19

    Abstract: Genomic analyses are commonly used to infer trends and broad rules underlying transcriptional control. The innovative approach by Tong et al. to interrogate genomic datasets allows extracting mechanistic information on the specific regulation of ... ...

    Abstract Genomic analyses are commonly used to infer trends and broad rules underlying transcriptional control. The innovative approach by Tong et al. to interrogate genomic datasets allows extracting mechanistic information on the specific regulation of individual genes.
    MeSH term(s) Beauty ; Gene Expression Regulation ; Genome ; Genomics ; Humans
    Language English
    Publishing date 2016-03-24
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2016.03.011
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  3. Article ; Online: Transcription factors as drivers of distinct pancreatic ductal adenocarcinoma (PDAC) programmes: a role for HNF4A.

    Diaferia, Giuseppe Riccardo / Natoli, Gioacchino

    Gut

    2020  Volume 70, Issue 5, Page(s) 816–817

    MeSH term(s) Carcinoma, Pancreatic Ductal/genetics ; Hepatocyte Nuclear Factor 4/genetics ; Humans ; Pancreatic Ducts ; Pancreatic Neoplasms/genetics ; Transcription Factors
    Chemical Substances HNF4A protein, human ; Hepatocyte Nuclear Factor 4 ; Transcription Factors
    Language English
    Publishing date 2020-10-01
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 80128-8
    ISSN 1468-3288 ; 0017-5749
    ISSN (online) 1468-3288
    ISSN 0017-5749
    DOI 10.1136/gutjnl-2020-322814
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  4. Article ; Online: Transcriptional repressors as guardians of tissue macrophage identity.

    Gualdrini, Francesco / Natoli, Gioacchino

    The EMBO journal

    2019  Volume 38, Issue 19, Page(s) e103271

    Abstract: The association between specific transcription factors (TFs) and defined tissue-specific macrophage phenotypes is far from being univocal. Many TFs that have been associated with tissue-specific macrophages have relatively broad expression profiles ... ...

    Abstract The association between specific transcription factors (TFs) and defined tissue-specific macrophage phenotypes is far from being univocal. Many TFs that have been associated with tissue-specific macrophages have relatively broad expression profiles suggesting the critical involvement of combinatorial regulation by multiple TFs in bringing about specific phenotypes. In the current issue of The EMBO Journal, Rauschmeier et al (2019) report the identification of the transcriptional repressors BHLHE40 and BHLHE41 as novel regulators of tissue-specific macrophage properties that work both to promote alveolar macrophage (AM) identity and to suppress alternative tissue-specific phenotypes.
    MeSH term(s) Macrophages ; Macrophages, Alveolar ; Phenotype ; Transcription Factors/genetics
    Chemical Substances Transcription Factors
    Language English
    Publishing date 2019-09-17
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 586044-1
    ISSN 1460-2075 ; 0261-4189
    ISSN (online) 1460-2075
    ISSN 0261-4189
    DOI 10.15252/embj.2019103271
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  5. Article ; Online: Tumor cell heterogeneity and its transcriptional bases in pancreatic cancer: a tale of two cell types and their many variants.

    Milan, Marta / Diaferia, Giuseppe R / Natoli, Gioacchino

    The EMBO journal

    2021  Volume 40, Issue 13, Page(s) e107206

    Abstract: Pancreatic ductal adenocarcinoma (PDAC), one of the most highly lethal tumors, is characterized by complex histology, with a massive fibrotic stroma in which both pseudo-glandular structures and compact nests of abnormally differentiated tumor cells are ... ...

    Abstract Pancreatic ductal adenocarcinoma (PDAC), one of the most highly lethal tumors, is characterized by complex histology, with a massive fibrotic stroma in which both pseudo-glandular structures and compact nests of abnormally differentiated tumor cells are embedded, in different proportions and with different mutual relationships in space. This complexity and the heterogeneity of the tumor component have hindered the development of a broadly accepted, clinically actionable classification of PDACs, either on a morphological or a molecular basis. Here, we discuss evidence suggesting that such heterogeneity can to a large extent, albeit not exclusively, be traced back to two main classes of PDAC cells that commonly coexist in the same tumor: cells that maintained their ability to differentiate toward endodermal, mucin-producing epithelia and epithelial cells unable to form glandular structures and instead characterized by various levels of squamous differentiation and the expression of mesenchymal lineage genes. The underlying gene regulatory networks and how they are controlled by distinct transcription factors, as well as the practical implications of these two different populations of tumor cells, are discussed.
    MeSH term(s) Animals ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/pathology ; Cell Differentiation/genetics ; Epithelial Cells/pathology ; Epithelium/pathology ; Gene Expression Regulation, Neoplastic/genetics ; Gene Regulatory Networks/genetics ; Humans ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Transcription Factors/genetics ; Transcription, Genetic/genetics
    Chemical Substances Transcription Factors
    Language English
    Publishing date 2021-04-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 586044-1
    ISSN 1460-2075 ; 0261-4189
    ISSN (online) 1460-2075
    ISSN 0261-4189
    DOI 10.15252/embj.2020107206
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  6. Article ; Online: Integration of transcriptional and metabolic control in macrophage activation.

    Natoli, Gioacchino / Pileri, Francesco / Gualdrini, Francesco / Ghisletti, Serena

    EMBO reports

    2021  Volume 22, Issue 9, Page(s) e53251

    Abstract: Macrophages react to microbial and endogenous danger signals by activating a broad panel of effector and homeostatic responses. Such responses entail rapid and stimulus-specific changes in gene expression programs accompanied by extensive rewiring of ... ...

    Abstract Macrophages react to microbial and endogenous danger signals by activating a broad panel of effector and homeostatic responses. Such responses entail rapid and stimulus-specific changes in gene expression programs accompanied by extensive rewiring of metabolism, with alterations in chromatin modifications providing one layer of integration of transcriptional and metabolic regulation. A systematic and mechanistic understanding of the mutual influences between signal-induced metabolic changes and gene expression is still lacking. Here, we discuss current evidence, controversies, knowledge gaps, and future areas of investigation on how metabolic and transcriptional changes are dynamically integrated during macrophage activation. The cross-talk between metabolism and inflammatory gene expression is in part accounted for by alterations in the production, usage, and availability of metabolic intermediates that impact the macrophage epigenome. In addition, stimulus-inducible gene expression changes alter the production of inflammatory mediators, such as nitric oxide, that in turn modulate the activity of metabolic enzymes thus determining complex regulatory loops. Critical issues remain to be understood, notably whether and how metabolic rewiring can bring about gene-specific (as opposed to global) expression changes.
    MeSH term(s) Gene Expression ; Gene Expression Regulation ; Humans ; Inflammation/genetics ; Macrophage Activation/genetics ; Macrophages
    Language English
    Publishing date 2021-07-30
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.15252/embr.202153251
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  7. Article ; Online: Adaptation and memory in immune responses.

    Natoli, Gioacchino / Ostuni, Renato

    Nature immunology

    2019  Volume 20, Issue 7, Page(s) 783–792

    Abstract: Adaptation is the ability of cells, tissues and organisms to rapidly and reversibly modify their properties to maximize fitness in a changing environment. The activity of immune-system components unfolds in the remarkably heterogeneous milieus to which ... ...

    Abstract Adaptation is the ability of cells, tissues and organisms to rapidly and reversibly modify their properties to maximize fitness in a changing environment. The activity of immune-system components unfolds in the remarkably heterogeneous milieus to which they are exposed in different tissues, during homeostasis or during various acute or chronic pathological states. Therefore, adaptation is essential for immune cells to tune their responses to a large variety of contexts and conditions. The adaptation of immune cells reflects the integration of multiple inputs acting simultaneously or in a temporal sequence, which eventually leads to transcriptional reprogramming and to various functional consequences, some of which extend beyond the duration of the stimulus. A range of adaptive responses have been observed in both adaptive immune cells and innate immune cells; these are referred to with terms such as 'plasticity', 'priming', 'training', 'exhaustion' and 'tolerance', among others, all of which can be useful for defining a certain immunological process or outcome but whose underlying molecular frameworks are often incompletely understood. Here we review and analyze mechanisms of adaptation and memory in immunity with the aim of providing basic concepts that rationalize the properties and molecular bases of these essential processes.
    MeSH term(s) Adaptation, Physiological ; Adaptive Immunity ; Animals ; Gene Expression Regulation ; Histones/metabolism ; Humans ; Hypersensitivity/immunology ; Immune System/cytology ; Immune System/immunology ; Immune System/metabolism ; Immune Tolerance ; Immunity ; Immunity, Innate ; Immunologic Memory ; Organ Specificity/immunology ; Phenotype ; Signal Transduction
    Chemical Substances Histones
    Language English
    Publishing date 2019-06-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-019-0399-9
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  8. Article: From the Beauty of Genomic Landscapes to the Strength of Transcriptional Mechanisms

    Natoli, Gioacchino

    Cell. 2016 Mar. 24, v. 165

    2016  

    Abstract: Genomic analyses are commonly used to infer trends and broad rules underlying transcriptional control. The innovative approach by Tong et al. to interrogate genomic datasets allows extracting mechanistic information on the specific regulation of ... ...

    Abstract Genomic analyses are commonly used to infer trends and broad rules underlying transcriptional control. The innovative approach by Tong et al. to interrogate genomic datasets allows extracting mechanistic information on the specific regulation of individual genes.
    Keywords data collection ; genes ; transcription (genetics)
    Language English
    Dates of publication 2016-0324
    Size p. 18-19.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2016.03.011
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  9. Article ; Online: Shiftworking keeps locked-down lab on track.

    Natoli, Gioacchino / Minucci, Saverio / Pelicci, Pier Giuseppe

    Nature

    2020  Volume 580, Issue 7805, Page(s) 590

    MeSH term(s) COVID-19 ; Contact Tracing ; Coronavirus Infections/diagnosis ; Coronavirus Infections/epidemiology ; Coronavirus Infections/prevention & control ; Disinfection ; Humans ; Italy/epidemiology ; Laboratories/organization & administration ; Occupational Health ; Pandemics/prevention & control ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/prevention & control ; Quarantine ; Research/economics ; Research/organization & administration ; Research Personnel/organization & administration ; Safety ; Shift Work Schedule
    Keywords covid19
    Language English
    Publishing date 2020-04-28
    Publishing country England
    Document type Letter
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-020-01268-x
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  10. Article ; Online: NF-κB and chromatin: ten years on the path from basic mechanisms to candidate drugs.

    Natoli, Gioacchino

    Immunological reviews

    2012  Volume 246, Issue 1, Page(s) 183–192

    Abstract: Release of nuclear factor κΒ (NF-κB) dimers from the inhibitors of NF-κΒ (IκBs) and their subsequent nuclear translocation are only the initial events leading to the induction of NF-κB-regulated genes. Once in the nucleus, NF-κB dimers must gain access ... ...

    Abstract Release of nuclear factor κΒ (NF-κB) dimers from the inhibitors of NF-κΒ (IκBs) and their subsequent nuclear translocation are only the initial events leading to the induction of NF-κB-regulated genes. Once in the nucleus, NF-κB dimers must gain access to their cognate sites in target genes. While some sites are found in a constitutively accessible state, many others are associated with nucleosomal histones in a manner that prevents NF-κB binding. Binding to such sites requires specific chromatin remodeling events driven by functionally cooperating transcription factors. Ten years of research on the complex interplay between chromatin and NF-κB led to some major successes, most notably the identification of the specific sequence features or trans-acting factors controlling the state of accessibility of κB sites, as well as the dissection of the mechanisms and players involved in the opening of occluded sites. Moreover, attempts at identifying mechanism-based compounds that inhibit the activation of selected subsets of NF-κB-dependent genes acting on chromatin-regulated transitions are starting to give initial promising results in preclinical tests.
    MeSH term(s) Animals ; Chromatin/metabolism ; Gene Expression Regulation/drug effects ; Histones/metabolism ; Humans ; Inflammation/genetics ; NF-kappa B/metabolism ; Nucleosomes/metabolism ; Regulatory Sequences, Nucleic Acid ; Transcription Factors/metabolism
    Chemical Substances Chromatin ; Histones ; NF-kappa B ; Nucleosomes ; Transcription Factors
    Language English
    Publishing date 2012-03
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/j.1600-065X.2012.01103.x
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