Polycomb/Trithorax group-dependent regulation of the neuronal gene Lim3 involved in Drosophila lifespan control

Publication date: Available online 17 March 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Olga Y. Rybina, Yakov M. Rozovsky, Ekaterina R. Veselkina, Elena G. Pasyukova
Molecular mechanisms governing gene expression and defining complex phenotypes are central to understanding the basics of development and aging. Here, we demonstrate that naturally occurring polymorphisms of the Lim3 regulatory region that are associated with variation in gene expression and Drosophila lifespan control are located exclusively in the Polycomb response element (PRE). We find that the Polycomb group (PcG) protein Polycomb (PC) is bound to the PRE only in embryos where Lim3 is present in both repressed and active states. In contrast, the Trithorax group (TrxG) protein absent, small, or homeotic discs 1 (ASH1) is bound downstream of the PRE, to a region adjacent to the Lim3 transcription start site in embryos and adult flies, in which Lim3 is in an active state. Furthermore, mutations in Pc and ash1 genes affect Lim3 expression depending on the structural integrity of the Lim3 PRE, thus confirming functional interactions between these proteins and Lim3 regulatory region. In addition, we demonstrate that the evolutionary conserved Lim3 core promoter provides basic Lim3 expression, whereas structural changes in the Lim3 PRE of distal promoter provide stage-, and tissue-specific Lim3 expression. Therefore, we hypothesize that PcG/TrxG proteins, which are directly involved in Lim3 transcription regulation, participate in lifespan control.



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Suberanilohydroxamic acid prevents TGF-β1-induced COX-2 repression in human lung fibroblasts post-transcriptionally by TIA-1 downregulation

Publication date: Available online 17 March 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Alice Pasini, Oliver J. Brand, Gisli Jenkins, Alan J. Knox, Linhua Pang
Cyclooxygenase-2 (COX-2), with its main antifibrotic metabolite PGE2, is regarded as an antifibrotic gene. Repressed COX-2 expression and deficient PGE2 have been shown to contribute to the activation of lung fibroblasts and excessive deposition of collagen in pulmonary fibrosis. We have previously demonstrated that COX-2 expression in lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) is epigenetically silenced and can be restored by epigenetic inhibitors. This study aimed to investigate whether COX-2 downregulation induced by the profibrotic cytokine transforming growth factor-β1 (TGF-β1) in normal lung fibroblasts could be prevented by epigenetic inhibitors. We found that COX-2 protein expression and PGE2 production were markedly reduced by TGF-β1 and this was prevented by the pan-histone deacetylase inhibitor suberanilohydroxamic acid (SAHA) and to a lesser extent by the DNA demethylating agent Decitabine (DAC), but not by the G9a histone methyltransferase (HMT) inhibitor BIX01294 or the EZH2 HMT inhibitor 3-deazaneplanocin A (DZNep). However, chromatin immunoprecipitation assay revealed that the effect of SAHA was unlikely mediated by histone modifications. Instead 3′-untranslated region (3′-UTR) luciferase reporter assay indicated the involvement of post-transcriptional mechanisms. This was supported by the downregulation by SAHA of the 3′-UTR mRNA binding protein TIA-1 (T-cell intracellular antigen-1), a negative regulator of COX-2 translation. Furthermore, TIA-1 knockdown by siRNA mimicked the effect of SAHA on COX-2 expression. These findings suggest SAHA can prevent TGF-β1-induced COX-2 repression in lung fibroblasts post-transcriptionally through a novel TIA-1-dependent mechanism and provide new insights into the mechanisms underlying its potential antifibrotic activity.Abbreviations



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Erratum: Behandlung im Voraus planen – Bedeutung für die Intensiv- und Notfallmedizin

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: e1-e1
DOI: 10.1055/a-0591-7094

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

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Quantification of upper limb position sense using an exoskeleton and a virtual reality display

Proprioceptive sense plays a significant role in the generation and correction of skilled movements and, consequently, in most activities of daily living. We developed a new proprioception assessment protocol ...

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AHA volunteer raises CPR awareness with campaign

Ron Mullins formed an ambassador group to inform the public about "Hands-only" CPR after two friends died because bystanders did not perform CPR

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Provider-Associated Measurement Error in Routine Outcome Monitoring in Community Mental Health

Abstract

Despite the strengths of routine outcome monitoring (ROM) in community mental health settings, there are a number of barriers to effective implementation of ROM, including measurement error due to provider factors (e.g., training level) and non-target client factors (i.e., client characteristics which have no meaningful relationship to the outcome of interest). In this study, ROM data from 80 client-provider dyads were examined for sources of variance due to provider factors and non-target client factors. Results indicated that provider factors and non-target client factors accounted for between 9.6 and 54% of the variance in the ROM measures. Our findings supported past research that provider characteristics impact ROM, and added the novel finding that client gender, age, diagnosis, and cognition also impact ROM. Methods to increase accuracy and utility of ROM in community mental health are discussed.

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