NET silencing by let-7i in postural tachycardia syndrome

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

doi:10.1172/jci.insight.90183

Cited by 18 publications

(14 citation statements)

References 47 publications

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“…Recently, using a novel assay-RNA of isolated chromatin combined with deep sequencing (RICh-seq)-we have identified microRNA Let-7i mediated NET gene suppression by MeCP2 in Postural tachycardia syndrome. 44 Because miRNA processing is a highly-regulated process it is not surprising to reveal that almost half of the MeCP2 bound microRNAs are altered in expression from KO mice show 35 and consistent with our experimental observations derived from RIP-seq. While this large dataset requires functional validation, our computational analysis supports the notion that the microRNAs may influence the capacity of MeCP2 to interact with chromatin to regulate gene expression.…”

Section: Discussionsupporting

confidence: 85%

MeCP2 interacts with chromosomal microRNAs in brain

et al. 2017

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Although methyl CpG binding domain protein-2 (MeCP2) is commonly understood to function as a silencing factor at methylated DNA sequences, recent studies also show that MeCP2 can bind unmethylated sequences and coordinate gene activation. MeCP2 displays broad binding patterns throughout the genome, with high expression levels similar to histone H1 in neurons. Despite its significant presence in the brain, only subtle gene expression changes occur in the absence of MeCP2. This may reflect a more complex regulatory mechanism of MeCP2 to complement chromatin binding. Using an RNA immunoprecipitation of native chromatin technique, we identify MeCP2 interacting microRNAs in mouse primary cortical neurons. In addition, comparison with mRNA sequencing data from Mecp2-null mice suggests that differentially expressed genes may indeed be targeted by MeCP2-interacting microRNAs. These findings highlight the MeCP2 interaction with microRNAs that may modulate its binding with chromatin and regulate gene expression.

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Section: Discussionsupporting

confidence: 85%

MeCP2 interacts with chromosomal microRNAs in brain

et al. 2017

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“…Histone deacetylase (HDAC) enzymes remove acetyl groups from histone tails. Thus, HAT/HDAC activity balance is an important determinant of gene regulation, and it has accordingly emerged as a potential therapeutic target for the treatment of various diseases (48,62,108,127). DNA methylation regulates gene expression.…”

Section: Chromatin Reorganization and Innate Immune Memorymentioning

confidence: 99%

Epigenetics and Trained Immunity

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Joosten

et al. 2018

Antioxidants & Redox Signaling

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“…The first, demonstrated in several disorders including essential hypertension, 71 involves preferential binding of the microRNA, miR-19a-3p, to a single-nucleotide polymorphism of the 3′ untranslated region of the NET gene. The second example of epigenetic silencing of the NET gene, demonstrable in postural tachycardia syndrome but not studied to date in hypertension, 72 involves binding of the corepressor MeCP2 (methyl CpG binding protein 2) with the microRNA, Let 7i, to the NET gene regulatory region. The broader circumstances which evoke this epigenetic NET gene suppression are totally unknown.…”

Section: Impaired Neuronal Noradrenaline Reuptakementioning

confidence: 99%