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      Epigenetic regulation by gut microbiota

      review-article
      ,
      Gut Microbes
      Taylor & Francis
      Microbiota, microbiome, epigenetics, epigenome, chromatin, intestine, histone modification, SCFAs, HDAC

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          ABSTRACT

          The gastrointestinal tract is continuously exposed to trillions of commensal microbes, collectively termed the microbiota, which are environmental stimuli that can direct health and disease within the host. In addition to well-established bacterial sensing pathways, microbial signals are also integrated through epigenetic modifications that calibrate the transcriptional program of host cells without altering the underlying genetic code. Microbiota-sensitive epigenetic changes include modifications to the DNA or histones, as well as regulation of non-coding RNAs. While microbiota-sensitive epigenetic mechanisms have been described in both local intestinal cells and as well in peripheral tissues, further research is required to fully decipher the complex relationship between the host and microbiota. This Review highlights current understandings of epigenetic regulation by gut microbiota and important implications of these findings in guiding therapeutic approaches to prevent or combat diseases driven by impaired microbiota-host interactions.

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          Most cited references101

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          Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation

          MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in regulating gene expression. The majority of miRNAs are transcribed from DNA sequences into primary miRNAs and processed into precursor miRNAs, and finally mature miRNAs. In most cases, miRNAs interact with the 3′ untranslated region (3′ UTR) of target mRNAs to induce mRNA degradation and translational repression. However, interaction of miRNAs with other regions, including the 5′ UTR, coding sequence, and gene promoters, have also been reported. Under certain conditions, miRNAs can also activate translation or regulate transcription. The interaction of miRNAs with their target genes is dynamic and dependent on many factors, such as subcellular location of miRNAs, the abundancy of miRNAs and target mRNAs, and the affinity of miRNA-mRNA interactions. miRNAs can be secreted into extracellular fluids and transported to target cells via vesicles, such as exosomes, or by binding to proteins, including Argonautes. Extracellular miRNAs function as chemical messengers to mediate cell-cell communication. In this review, we provide an update on canonical and non-canonical miRNA biogenesis pathways and various mechanisms underlying miRNA-mediated gene regulations. We also summarize the current knowledge of the dynamics of miRNA action and of the secretion, transfer, and uptake of extracellular miRNAs.
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            The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.

            Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota-derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
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              Gene regulation by long non-coding RNAs and its biological functions

              Evidence accumulated over the past decade shows that long non-coding RNAs (lncRNAs) are widely expressed and have key roles in gene regulation. Recent studies have begun to unravel how the biogenesis of lncRNAs is distinct from that of mRNAs and is linked with their specific subcellular localizations and functions. Depending on their localization and their specific interactions with DNA, RNA and proteins, lncRNAs can modulate chromatin function, regulate the assembly and function of membraneless nuclear bodies, alter the stability and translation of cytoplasmic mRNAs and interfere with signalling pathways. Many of these functions ultimately affect gene expression in diverse biological and physiopathological contexts, such as in neuronal disorders, immune responses and cancer. Tissue-specific and condition-specific expression patterns suggest that lncRNAs are potential biomarkers and provide a rationale to target them clinically. In this Review, we discuss the mechanisms of lncRNA biogenesis, localization and functions in transcriptional, post-transcriptional and other modes of gene regulation, and their potential therapeutic applications.
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                Author and article information

                Journal
                Gut Microbes
                Gut Microbes
                Gut Microbes
                Taylor & Francis
                1949-0976
                1949-0984
                9 January 2022
                2022
                9 January 2022
                : 14
                : 1
                : 2022407
                Affiliations
                [0001]Division of Immunobiology and Center for Inflammation and Tolerance, Cincinnati Children’s Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine; , Cincinnati, OH, USA
                Author notes
                CONTACT Theresa Alenghat theresa.alenghat@ 123456cchmc.org Division of Immunobiology and Center for Inflammation and Tolerance, Cincinnati Children’s Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine; , Cincinnati, OH, USA
                Author information
                https://orcid.org/0000-0003-4514-3710
                Article
                2022407
                10.1080/19490976.2021.2022407
                8744890
                35000562
                be6fcc3c-48ed-4580-89d8-c441b2d92ef2
                © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 1, References: 101, Pages: 1
                Categories
                Review
                Review

                Microbiology & Virology
                microbiota,microbiome,epigenetics,epigenome,chromatin,intestine,histone modification,scfas,hdac

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