title: A TEAD1/p65 complex regulates the eutherian-conserved MnSOD intronic enhancer, eRNA transcription and the innate immune response.
abstract: Manganese superoxide dismutase (MnSOD), a critical anti-oxidant enzyme, detoxifies the mitochondrial-derived reactive oxygen species, superoxide, elicited through normal respiration or the inflammatory response. Proinflammatory stimuli induce MnSOD gene expression through a eutherian-conserved, intronic enhancer element. We identified two prototypic enhancer binding proteins, TEAD1 and p65, that when co-expressed induce MnSOD expression comparable to pro-inflammatory stimuli. TEAD1 causes the nuclear sequestration of p65 leading to a novel TEAD1/p65 complex that associates with the intronic enhancer and is necessary for cytokine induction of MnSOD. Unlike typical NF-κB-responsive genes, the induction of MnSOD does not involve p50. Beyond MnSOD, the TEAD1/p65 complex regulates a subset of genes controlling the innate immune response that were previously viewed as solely NF-κB-dependent. We also identified an enhancer-derived RNA (eRNA) that is induced by either proinflammatory stimuli or the TEAD1/p65 complex, potentially linking the intronic enhancer to intra- and interchromosomal gene regulation through the inducible eRNA.
authors: Departments of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors: Ann L
authors: AL
authors: Chokas
authors: Departments of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors: Justin S
authors: JS
authors: Bickford
authors: Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors: Sarah J
authors: SJ
authors: Barilovits
authors: Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Anesthesiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors: Richard J
authors: RJ
authors: Rogers
authors: Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors: Xiaolei
authors: X
authors: Qiu
authors: Departments of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors: Kimberly J
authors: KJ
authors: Newsom
authors: Departments of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors: Dawn E
authors: DE
authors: Beachy
authors: Departments of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, USA; Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL 32610, USA. Electronic address: hnick@ufl.edu.
authors: Harry S
authors: HS
authors: Nick
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007438:Introns; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000235:genetics*; D000091262:TEA Domain Transcription Factors; D051996:Transcription Factor RelA / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D051996:Transcription Factor RelA; D014157:Transcription Factors; D012313:RNA; D013482:Superoxide Dismutase
keywords: Enhancer-derived RNA (eRNA); Intronic enhancer; Manganese superoxide dismutase (MnSOD); TEAD1; p65