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@ARTICLE{Brunialti:270813,
      author       = {Brunialti, Electra and Rizzi, Nicoletta and Pinto-Costa,
                      Rita and Villa, Alessandro and Panzeri, Alessia and Meda,
                      Clara and Rebecchi, Monica and Di Monte, Donato A and Ciana,
                      Paolo},
      title        = {{D}esign and validation of a reporter mouse to study the
                      dynamic regulation of {TFEB} and {TFE}3 activity through in
                      vivo imaging techniques.},
      journal      = {Autophagy},
      volume       = {20},
      number       = {8},
      issn         = {1554-8627},
      address      = {Abingdon, Oxon},
      publisher    = {Taylor $\&$ Francis},
      reportid     = {DZNE-2024-00903},
      pages        = {1879 - 1894},
      year         = {2024},
      note         = {ISSN 1554-8635 not unique: **2 hits**.},
      abstract     = {TFEB and TFE3 belong to the MiT/TFE family of transcription
                      factors that bind identical DNA responsive elements in the
                      regulatory regions of target genes. They are involved in
                      regulating lysosomal biogenesis, function, exocytosis,
                      autophagy, and lipid catabolism. Precise control of TFEB and
                      TFE3 activity is crucial for processes such as senescence,
                      stress response, energy metabolism, and cellular catabolism.
                      Dysregulation of these factors is implicated in various
                      diseases, thus researchers have explored pharmacological
                      approaches to modulate MiT/TFE activity, considering these
                      transcription factors as potential therapeutic targets.
                      However, the physiological complexity of their functions and
                      the lack of suitable in vivo tools have limited the
                      development of selective MiT/TFE modulating agents. Here, we
                      have created a reporter-based biosensor, named
                      CLEARoptimized, facilitating the pharmacological profiling
                      of TFEB- and TFE3-mediated transcription. This innovative
                      tool enables the measurement of TFEB and TFE3 activity in
                      living cells and mice through imaging and biochemical
                      techniques. CLEARoptimized consists of a promoter with six
                      coordinated lysosomal expression and regulation motifs
                      identified through an in-depth bioinformatic analysis of the
                      promoters of 128 TFEB-target genes. The biosensor drives the
                      expression of luciferase and tdTomato reporter genes,
                      allowing the quantification of TFEB and TFE3 activity in
                      cells and in animals through optical imaging and biochemical
                      assays. The biosensor's validity was confirmed by modulating
                      MiT/TFE activity in both cell culture and reporter mice
                      using physiological and pharmacological stimuli. Overall,
                      this study introduces an innovative tool for studying
                      autophagy and lysosomal pathway modulation at various
                      biological levels, from individual cells to the entire
                      organism.Abbreviations: CLEAR: coordinated lysosomal
                      expression and regulation; MAR: matrix attachment regions;
                      MiT: microphthalmia-associated transcription factor; ROI:
                      region of interest; TBS: tris-buffered saline; TF:
                      transcription factor; TFE3: transcription factor binding to
                      IGHM enhancer 3; TFEB: transcription factor EB; TH: tyrosine
                      hydroxylase; TK: thymidine kinase; TSS: transcription start
                      site.},
      keywords     = {Animals / Basic Helix-Loop-Helix Leucine Zipper
                      Transcription Factors: metabolism / Mice / Lysosomes:
                      metabolism / Genes, Reporter / Humans / Promoter Regions,
                      Genetic: genetics / Autophagy / Biosensing Techniques:
                      methods / Gene Expression Regulation: drug effects /
                      Autophagy (Other) / drug discovery (Other) / luciferase
                      (Other) / lysosomal pathway (Other) / non-invasive study of
                      TFEB and TFE3 (Other) / optical imaging (Other) / Basic
                      Helix-Loop-Helix Leucine Zipper Transcription Factors (NLM
                      Chemicals) / Tcfeb protein, mouse (NLM Chemicals) / Tcfe3
                      protein, mouse (NLM Chemicals) / TFE3 protein, human (NLM
                      Chemicals) / TFEB protein, human (NLM Chemicals)},
      cin          = {AG Di Monte},
      ddc          = {570},
      cid          = {I:(DE-2719)1013008},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC11262230},
      pubmed       = {pmid:38522425},
      doi          = {10.1080/15548627.2024.2334111},
      url          = {https://pub.dzne.de/record/270813},
}