LitCovid-sample-sentences  

PMC:7556165 / 10685-18354 JSONTXT 18 Projects

Annnotations TAB TSV DIC JSON TextAE-old TextAE

Id Subject Object Predicate Lexical cue
T74 0-80 Sentence denotes Transcriptional, Post-transcriptional, and Post-translational Regulation of ACE2
T75 81-364 Sentence denotes The location of the ACE2 gene on the X chromosome questions whether one of the two ACE2 is silenced in females, to balance female/male expression dosage (X chromosome inactivation or XCI), or otherwise belongs to the class of “escape genes” which are transcribed on both chromosomes.
T76 365-553 Sentence denotes Interestingly, a wide survey of XCI in several individuals and tissues showed that ACE2 is a heterogeneous escape gene, because it has a tissue-dependent sex bias (Tukiainen et al., 2017).
T77 554-706 Sentence denotes A growing number of recent findings point to an important role of epigenetic mechanisms associated with several human diseases (Surguchov et al., 2017).
T78 707-881 Sentence denotes In this context, several authors highlighted the regulatory role of 17β-estradiol (E2), a primary female sex steroid, in the expression of ACE2 in a tissue-dependent fashion.
T79 882-1030 Sentence denotes Liu et al. (2010) and Stelzig et al. (2020) found out that E2 downregulates ACE2 in kidney and differentiated airway epithelial cells, respectively.
T80 1031-1313 Sentence denotes The latter result is particularly important, as the male-bias of ACE2 expression in the lung could account for the alleged higher susceptibility of males to COVID-19 symptoms following ACE2-dependent SARS-CoV-2 infection (section Links Between ACE2 and COVID-19) (Jin et al., 2020).
T81 1314-1486 Sentence denotes Yet, Bukowska et al. (2017) observed that E2 increases ACE2 transcription and expression in human atrial tissue, while at the same time depressing the level of ACE protein.
T82 1487-1698 Sentence denotes This mechanism attenuates the renin-angiotensin system and, in tandem with anti-inflammatory and anti-oxidative effects, enables a stronger response to myocardial stress and contributes to antiarhythmic effects.
T83 1699-1845 Sentence denotes The upregulation of ACE2 (and downregulation of ACE) was clearly linked to binding of E2 to Estrogen Receptor alpha (ERα) (Bukowska et al., 2017).
T84 1846-2086 Sentence denotes The E2-ERα complex might migrate to the nucleus to bind to estrogen response elements, although the actual mechanism is still obscure and should likely involve other co-factors to take into account the observed tissue bias of E2 regulation.
T85 2087-2336 Sentence denotes Nonetheless, it was demonstrated that the Estrogen Related Receptor alpha (ERRα), which likewise ERα recognizes the estrogen response element in target genes, binds to ACE2 promoter to repress transcription (Tremblay et al., 2010; Lee et al., 2012).
T86 2337-2439 Sentence denotes Hopefully, future studies will shed more light on the intriguing role of estrogens in ACE2 regulation.
T87 2440-2602 Sentence denotes A recent analysis of public genomic and transcriptomic data outlined the role of histone methylation, a classical epigenetic mark, to regulate ACE2 transcription.
T88 2603-2764 Sentence denotes Indeed, Li Y. et al. (2020) showed that transcription of ACE2 was significantly upregulated when the histone mutant H3K27M was overexpressed to inhibit H3K27me3.
T89 2765-2847 Sentence denotes Conversely, overexpression of mutant H3K4/9/36M did not change ACE2 transcription.
T90 2848-3003 Sentence denotes Trimethylation of K27 on H3 is catalyzed by the polycomb groups (PcG), a group of conserved transcriptional gene repressors (Schuettengruber et al., 2017).
T91 3004-3066 Sentence denotes PcG proteins assemble into two major complexes: PRC1 and PRC2.
T92 3067-3191 Sentence denotes The simplest model of PcG activity involves trimethylation of H3 by PRC2 at target gene promoters (Blackledge et al., 2015).
T93 3192-3440 Sentence denotes These epigenetic marks recruit PRC1 on DNA, which in turn acts as E3-ligase and ubiquitinates nearby H2A histones (Storti et al., 2019), triggering silencing of gene transcription by local and reversible compaction of chromatin (Illingworth, 2019).
T94 3441-3506 Sentence denotes The catalytic subunit of PRC2 is constituted by the EZH2 protein.
T95 3507-3674 Sentence denotes In agreement with the inverse correlation between ACE2 level and H3K27me3, ACE2 expression in human ESCs was upregulated following EZH2 knock-out (Li Y. et al., 2020).
T96 3675-3738 Sentence denotes On the other side, recovery of EZH2 restored basal ACE2 levels.
T97 3739-3932 Sentence denotes Chromatin immunoprecipitation sequencing (ChIP-seq) showed that EZH2 depletion induced H3K27me3 decrease, with concomitant H3K27ac increase, at ACE2 promoter in human ESCs (Li Y. et al., 2020).
T98 3933-4219 Sentence denotes The role of H3 methylation and acetylation in the epigenetic regulation of ACE2 was also hypothesized by Pinto et al., who demonstrated that co-morbidities such as hypertension, diabetes, and chronic obstructive lung disease increase ACE2 transcription in the lung (Pinto et al., 2020).
T99 4220-4301 Sentence denotes Histone methylation does not appear to exhaust the epigenetic regulation of ACE2.
T100 4302-4450 Sentence denotes Notably, the NAD+-dependent deacetylase SIRT1 binds to ACE2 promoter favoring its transcription during cellular energy stress (Clarke et al., 2014).
T101 4451-4531 Sentence denotes Two recent unrefereed preprints highlighted other epigenetic mechanisms at play.
T102 4532-4736 Sentence denotes Corley et al.1 pointed out that DNA methylation across three CpG islands in the ACE2 promoter was lower in lung epithelial cells compared to other cell types, suggesting high transcription in lung tissue.
T103 4737-4939 Sentence denotes These findings are in excellent agreement with the reported inverse correlation between ACE2 transcription and promoter methylation in tumors, which will be discussed in section ACE2 and Other Diseases.
T104 4940-5122 Sentence denotes This correlation is also supported by the observation that in children ACE2 is normally hypermethylated and poorly expressed either in the lung and in other organs (Pruimboom, 2020).
T105 5123-5344 Sentence denotes Glinsky (2020) addressed the epigenetic role of Vitamin D on ACE2 expression, showing by gene set enrichment analysis that the Vitamin D receptor (VDR) should be involved in a set of regulatory pathways conveying on ACE2.
T106 5345-5554 Sentence denotes More specifically, VDR activation would downregulate ACE2, thus affording a potential reason for the alleged beneficial role of Vitamin D in COVID-19 (section ACE2 and the Inflammatory Response to Sars-CoV-2).
T107 5555-5674 Sentence denotes Finally, the strict homeostatic balance of ACE/ACE2 activities suggests transcriptional co-regulation of both proteins.
T108 5675-5970 Sentence denotes Remarkably, Yang et al. (2016) have demonstrated that a subtle regulatory mechanism acts in cardiac endothelial cells, where the Brg1 chromatin remodeler and the FoxM1 transcription factor cooperate to determine the ACE2/ACE expression ratio, particularly under cardiac hypertrophy of the heart.
T109 5971-6015 Sentence denotes Further regulation occurs at the mRNA level.
T110 6016-6141 Sentence denotes From putative microRNA-binding sites identified in vitro, Lambert et al. (2014) demonstrated that miR-421 downregulates ACE2.
T111 6142-6289 Sentence denotes According to the hypothesized mechanism, miR-421 modulates ACE2 expression by hampering translation rather than by degradation of mRNA transcripts.
T112 6290-6505 Sentence denotes Beside undergoing post-translational modifications by glycosylation and phosphorylation, ACE2 is also post-translationally regulated by shedding from cell membrane through the action of the metalloproteinase ADAM17.
T113 6506-6676 Sentence denotes The proteolysis of ACE2 releases a soluble, enzymatically active form which corresponds to the ACE2 ectodomain (Jia et al., 2009; Xiao et al., 2014; Conrad et al., 2016).
T114 6677-6794 Sentence denotes The function, if any, of soluble ACE2 is still obscure, but the shedding mechanism is under strict molecular control.
T115 6795-6957 Sentence denotes Lambert et al. (2008) highlighted that calmodulin associates with ACE2 to prevent its shedding, while calmodulin inhibitors increase the cellular release of ACE2.
T116 6958-7007 Sentence denotes Patel identified a positive feedback in the RAAS:
T117 7008-7118 Sentence denotes Ang II activates ADAM17, thereby increasing the release of ACE2, its negative regulator (Patel et al., 2016b).
T118 7119-7250 Sentence denotes It is worth noting that high levels of plasma-soluble ACE2 have been associated with myocardial dysfunction (Epelman et al., 2009).
T119 7251-7382 Sentence denotes The potential pathophysiological role of ADAM17 is further discussed in paragraph ACE2 and the Inflammatory Response to Sars-CoV-2.
T120 7383-7503 Sentence denotes Figure 2 summarizes the known transcriptional, post-transcriptional, and post translational regulation pathways of ACE2.
T121 7504-7605 Sentence denotes FIGURE 2 Regulation pathways of transcription, translation, and post-translational shedding of ACE2.
T122 7606-7638 Sentence denotes Red text: non-molecular factors.
T123 7639-7669 Sentence denotes Black text: molecular factors.