NET silencing by let-7i in postural tachycardia syndrome
Abdul Waheed Khan, … , Murray D. Esler, Assam El-Osta
Abdul Waheed Khan, … , Murray D. Esler, Assam El-Osta
Published March 23, 2017
Citation Information: JCI Insight. 2017;2(6):e90183. https://doi.org/10.1172/jci.insight.90183.
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Research Article Cardiology

NET silencing by let-7i in 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 that let-7i miRNA suppresses NET by methyl-CpG-binding protein 2 (MeCP2). Vorinostat restores epigenetic control and NET expression in leukocytes derived from POTS participants.

Authors

Abdul Waheed Khan, Mark Ziemann, Susan J. Corcoran, Harikrishnan K.N, Jun Okabe, Haloom Rafehi, Scott S. Maxwell, Murray D. Esler, Assam El-Osta

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Figure 2

RICh-seq identifies NET promoter–specific RNAs.

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RICh-seq identifies NET promoter–specific RNAs. RNA of isolated chromati...
RNA of isolated chromatin (RICh) combined with massive parallel sequencing (RICh-seq) was undertaken to identify norepinephrine transporter (NET) promoter–specific RNAs. (A) MA plots of RNA detected at the NET promoter compared with input RNA (total chromatin-bound RNA) and scrambled-probe controls. *Red data points indicate FDR < 0.05. (B) A stacked bar chart showing RNA classes detected by RICh-seq in the input and scrambled datasets. (C) A heatmap showing k-means clustering based on the log(fold change) (logFC) of RNA transcripts enriched at the NET promoter with an FDR < 0.05 in at least 1 comparison. RNAs with FDR < 0.05 in both comparisons are highlighted in bold; n = 3. Mt, mitochondrial; snoRNA, small nucleolar RNA; snRNA, small nuclear RNA; misc RNA, miscellaneous RNA; scr, scramble; lincRNA, long intergenic noncoding RNA.