IntroductionA novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was recently identified as the pathogen responsible for the COVID-19 MESHD
outbreak. SARS-CoV-2 triggers severe pneumonia MESHD
, which leads to acute respiratory distress syndrome MESHD
and death MESHD
in severe cases. As reported, SARS-CoV-2 is 80% genetically identical to the 2003 SARS-CoV virus MESHD
. Angiotensin-converting enzyme 2 HGNC
( ACE2 HGNC
) has been identified as the main receptor for entry of both SARS-CoV MESHD
and SARS-CoV-2 into human cells. ACE2 HGNC
is normally expressed in cardiovascular and lung type II alveolar epithelial MESHD
cells, where it positively modulates the RAS system that regulates blood flow, pressure, and fluid homeostasis. Thus, virus-induced reduction of ACE2 HGNC
gene expression is considered to make a significant contribution to severe acute respiratory failure MESHD
. Chromatin remodeling plays a significant role in the regulation of ACE2 HGNC
gene expression and the activity of regulatory elements within the genome.
MethodsHere, we integrated data on physical chromatin interactions within the genome organization (captured by Hi-C) with tissue-specific gene expression data to identify spatial expression quantitative trait loci (eQTLs) and thus regulatory elements located within the ACE2 HGNC
ResultsWe identified regulatory elements within ACE2 HGNC
that control the expression of PIR HGNC
, CA5B HGNC
, and VPS13C HGNC
in the lung. The gene products of these genes are involved in inflammatory responses, de novo pyrimidine and polyamine synthesis, and the endoplasmic reticulum, respectively.
ConclusionOur study, although limited by the fact that the identification of the regulatory interactions is putative until proven by targeted experiments, supports the hypothesis that viral silencing of ACE2 HGNC
alters the activity of gene regulatory regions and promotes an intra-cellular environment suitable for viral replication.