title: NETsilencing bylet-7iin postural tachycardia syndrome.
abstract: While strongly implicated in postural tachycardia syndrome (POTS), considerable controversy exists regarding norepinephrine transporter (NET) loss of function. POTS is characterized by the clinical symptoms of orthostatic intolerance, lightheadedness, tachycardia, and syncope or near syncope with upright posture. Abnormal sympathetic nervous system activity is typical, of a type which suggests dysfunction of the NET, with evidence that the gene responsible is under tight epigenetic control. Using RNA of isolated chromatin combined with massive parallel sequencing (RICh-seq) we show thatlet-7imiRNA suppressesNETby methyl-CpG-binding protein 2 (MeCP2). Vorinostat restores epigenetic control andNETexpression in leukocytes derived from POTS participants.
authors.affiliation: Central Clinical School, Faculty of Medicine, Monash University, Victoria, Australia.|Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia.|Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Abdul Waheed
authors.initials: AW
authors.lastname: Khan
authors.affiliation: Central Clinical School, Faculty of Medicine, Monash University, Victoria, Australia.|Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Ziemann
authors.affiliation: Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Corcoran
authors.affiliation: Central Clinical School, Faculty of Medicine, Monash University, Victoria, Australia.|Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia.|Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Harikrishnan
authors.initials: H
authors.lastname: K N
authors.affiliation: Central Clinical School, Faculty of Medicine, Monash University, Victoria, Australia.|Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia.
authors.forename: Jun
authors.initials: J
authors.lastname: Okabe
authors.affiliation: Central Clinical School, Faculty of Medicine, Monash University, Victoria, Australia.|Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia.
authors.forename: Haloom
authors.initials: H
authors.lastname: Rafehi
authors.affiliation: Central Clinical School, Faculty of Medicine, Monash University, Victoria, Australia.|Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia.
authors.forename: Scott S
authors.initials: SS
authors.lastname: Maxwell
authors.affiliation: Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia.
authors.forename: Murray D
authors.initials: MD
authors.lastname: Esler
authors.affiliation: Central Clinical School, Faculty of Medicine, Monash University, Victoria, Australia.|Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia.|Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.|Hong Kong Institute of Diabetes and Obesity, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Assam
authors.initials: A
authors.lastname: El-Osta
mesh_terms: D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D020868:Gene Silencing; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D054972:Postural Orthostatic Tachycardia Syndrome / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D000077337:Vorinostat / Q000494:pharmacology
chemical_list: D056572:Histone Deacetylase Inhibitors; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D035683:MicroRNAs; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; C487931:mirnlet7 microRNA, human; D000077337:Vorinostat