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Article ; Online: Epigenetic regulation of ACE2, the receptor of the SARS-CoV-2 virus

Beacon, Tasnim H / Delcuve, Geneviève P / Davie, James R

2020 Volume 64, Issue 4, Page(s) 386–399

Abstract: The angiotensin-converting enzyme 2 (ACE2) is the receptor for the three coronaviruses HCoV-NL63, SARS-CoV, and SARS-CoV-2. ACE2 is involved in the regulation of the renin-angiotensin system and blood pressure. ACE2 is also involved in the regulation of ... ...

Abstract	The angiotensin-converting enzyme 2 (ACE2) is the receptor for the three coronaviruses HCoV-NL63, SARS-CoV, and SARS-CoV-2. ACE2 is involved in the regulation of the renin-angiotensin system and blood pressure. ACE2 is also involved in the regulation of several signaling pathways, including integrin signaling.
MeSH term(s)	Angiotensin-Converting Enzyme 2/genetics ; COVID-19 ; Epigenesis, Genetic ; Gene Expression Regulation ; Humans ; Promoter Regions, Genetic ; Protein Processing, Post-Translational ; Receptors, Virus/genetics ; Renin-Angiotensin System ; SARS-CoV-2 ; Signal Transduction
Chemical Substances	Receptors, Virus ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Keywords	covid19
Language	English
Publishing date	2020-10-21
Publishing country	Canada
Document type	Journal Article ; Review
ZDB-ID	639031-6
ISSN	1480-3321 ; 0831-2796
ISSN (online)	1480-3321
ISSN	0831-2796
DOI	10.1139/gen-2020-0124
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Epigenetic regulation of ACE2, the receptor of the SARS-CoV-2 virus

Beacon, Tasnim H / Delcuve, Geneviève P / Davie, James R

Genome

Abstract: The angiotensin-converting enzyme 2 (ACE2) is the receptor for the three coronaviruses HCoV-NL63, SARS-CoV and SARS-CoV-2. ACE2 is involved in the regulation of the renin-angiotensin system and blood pressure. ACE2 is also involved in the regulation of ... ...

Abstract	The angiotensin-converting enzyme 2 (ACE2) is the receptor for the three coronaviruses HCoV-NL63, SARS-CoV and SARS-CoV-2. ACE2 is involved in the regulation of the renin-angiotensin system and blood pressure. ACE2 is also involved in the regulation of several signaling pathways, including integrin signaling. ACE2 expression is regulated transcriptionally and post-transcriptionally. The expression of the gene is regulated by two promoters, with usage varying among tissues. ACE2 expression is greatest in the small intestine, kidney and heart and detectable in a variety of tissues and cell types. Herein we review the chemical and mechanical signal transduction pathways regulating the expression of the ACE2 gene and the epigenetic/chromatin features of the expressed gene.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #885889
Database	COVID19

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Article ; Online: SARS-CoV-2 multifaceted interaction with the human host. Part II: Innate immunity response, immunopathology, and epigenetics.

Beacon, Tasnim H / Su, Ruey-Chyi / Lakowski, Ted M / Delcuve, Geneviève P / Davie, James R

IUBMB life

2020 Volume 72, Issue 11, Page(s) 2331–2354

Abstract: The SARS-CoV-2 makes its way into the cell via the ACE2 receptor and the proteolytic action of TMPRSS2. In response to the SARS-CoV-2 infection, the innate immune response is the first line of defense, triggering multiple signaling pathways to produce ... ...

Abstract	The SARS-CoV-2 makes its way into the cell via the ACE2 receptor and the proteolytic action of TMPRSS2. In response to the SARS-CoV-2 infection, the innate immune response is the first line of defense, triggering multiple signaling pathways to produce interferons, pro-inflammatory cytokines and chemokines, and initiating the adaptive immune response against the virus. Unsurprisingly, the virus has developed strategies to evade detection, which can result in delayed, excessive activation of the innate immune system. The response elicited by the host depends on multiple factors, including health status, age, and sex. An overactive innate immune response can lead to a cytokine storm, inflammation, and vascular disruption, leading to the vast array of symptoms exhibited by COVID-19 patients. What is known about the expression and epigenetic regulation of the ACE2 gene and the various players in the host response are explored in this review.
MeSH term(s)	Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/immunology ; COVID-19/genetics ; COVID-19/immunology ; COVID-19/virology ; Cytokine Release Syndrome/genetics ; Cytokine Release Syndrome/immunology ; Cytokine Release Syndrome/virology ; Cytokines/genetics ; Cytokines/immunology ; Epigenesis, Genetic ; Gene Expression Regulation ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Immunity, Innate ; Interferons/genetics ; Interferons/immunology ; Receptors, Virus/genetics ; Receptors, Virus/immunology ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Serine Endopeptidases/genetics ; Serine Endopeptidases/immunology ; Signal Transduction ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology ; Virus Internalization ; Virus Replication
Chemical Substances	Cytokines ; Receptors, Virus ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Interferons (9008-11-1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
Keywords	covid19
Language	English
Publishing date	2020-09-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1492141-8
ISSN	1521-6551 ; 1521-6543
ISSN (online)	1521-6551
ISSN	1521-6543
DOI	10.1002/iub.2379
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1611: Show issues

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Article ; Online: SARS-CoV-2 multifaceted interaction with human host. Part I: What we have learnt and done so far, and the still unknown realities.

Delcuve, Geneviève P / Lakowski, Ted M / Su, Ruey-Chyi / Beacon, Tasnim H / Davie, James R

IUBMB life

2020 Volume 72, Issue 11, Page(s) 2313–2330

Abstract: SARS-CoV-2, the causing agent of the ongoing COVID-19 pandemic, is a beta-coronavirus which has 80% genetic homology with SARS-CoV, but displays increased virulence and transmissibility. Initially, SARS-CoV-2 was considered a respiratory virus generally ... ...

Abstract	SARS-CoV-2, the causing agent of the ongoing COVID-19 pandemic, is a beta-coronavirus which has 80% genetic homology with SARS-CoV, but displays increased virulence and transmissibility. Initially, SARS-CoV-2 was considered a respiratory virus generally causing a mild disease, only severe and fatal in the elderly and individuals with underlying conditions. Severe illnesses and fatalities were attributed to a cytokine storm, an excessive response from the host immune system. However, with the number of infections over 10 millions and still soaring, the insidious and stealthy nature of the virus has emerged, as it causes a vast array of diverse unexpected symptoms among infected individuals, including the young and healthy. It has become evident that besides infecting the respiratory tract, SARS-CoV-2 can affect many organs, possibly through the infection of the endothelium. This review presents an overview of our learning curve with the novel virus emergence, transmission, pathology, biological properties and host-interactions. It also briefly describes remedial measures taken until an effective vaccine is available, that is non-pharmaceutical interventions to reduce the viral spread and the repurposing of existing drugs, approved or in development for other conditions to eliminate the virus or mitigate the cytokine storm.
MeSH term(s)	Anti-Inflammatory Agents/therapeutic use ; Anticoagulants/therapeutic use ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; COVID-19/immunology ; COVID-19/virology ; Cytokine Release Syndrome/drug therapy ; Cytokine Release Syndrome/immunology ; Cytokine Release Syndrome/virology ; Drug Repositioning/methods ; Genome, Viral ; Host-Pathogen Interactions/drug effects ; Host-Pathogen Interactions/genetics ; Host-Pathogen Interactions/immunology ; Humans ; Immunologic Factors/therapeutic use ; Inflammation ; Masks ; Physical Distancing ; SARS Virus/drug effects ; SARS Virus/immunology ; SARS Virus/pathogenicity ; SARS-CoV-2/drug effects ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Severe Acute Respiratory Syndrome
Chemical Substances	Anti-Inflammatory Agents ; Anticoagulants ; Antiviral Agents ; Immunologic Factors
Keywords	covid19
Language	English
Publishing date	2020-09-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1492141-8
ISSN	1521-6551 ; 1521-6543
ISSN (online)	1521-6551
ISSN	1521-6543
DOI	10.1002/iub.2380
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1611: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: The dynamic broad epigenetic (H3K4me3, H3K27ac) domain as a mark of essential genes.

Beacon, Tasnim H / Delcuve, Geneviève P / López, Camila / Nardocci, Gino / Kovalchuk, Igor / van Wijnen, Andre J / Davie, James R

Clinical epigenetics

2021 Volume 13, Issue 1, Page(s) 138

Abstract: Transcriptionally active chromatin is marked by tri-methylation of histone H3 at lysine 4 (H3K4me3) located after first exons and around transcription start sites. This epigenetic mark is typically restricted to narrow regions at the 5`end of the gene ... ...

Abstract	Transcriptionally active chromatin is marked by tri-methylation of histone H3 at lysine 4 (H3K4me3) located after first exons and around transcription start sites. This epigenetic mark is typically restricted to narrow regions at the 5`end of the gene body, though a small subset of genes have a broad H3K4me3 domain which extensively covers the coding region. Although most studies focus on the H3K4me3 mark, the broad H3K4me3 domain is associated with a plethora of histone modifications (e.g., H3 acetylated at K27) and is therein termed broad epigenetic domain. Genes marked with the broad epigenetic domain are involved in cell identity and essential cell functions and have clinical potential as biomarkers for patient stratification. Reducing expression of genes with the broad epigenetic domain may increase the metastatic potential of cancer cells. Enhancers and super-enhancers interact with the broad epigenetic domain marked genes forming a hub of interactions involving nucleosome-depleted regions. Together, the regulatory elements coalesce with transcription factors, chromatin modifying/remodeling enzymes, coactivators, and the Mediator and/or Integrator complex into a transcription factory which may be analogous to a liquid-liquid phase-separated condensate. The broad epigenetic domain has a dynamic chromatin structure which supports frequent transcription bursts. In this review, we present the current knowledge of broad epigenetic domains.
MeSH term(s)	Epigenesis, Genetic/genetics ; Epigenesis, Genetic/physiology ; Genes, Essential/genetics ; Histone Code/genetics ; Histones/analysis ; Histones/genetics ; Humans
Chemical Substances	Histones
Language	English
Publishing date	2021-07-08
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2553921-8
ISSN	1868-7083 ; 1868-7075
ISSN (online)	1868-7083
ISSN	1868-7075
DOI	10.1186/s13148-021-01126-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Histone H3K4 trimethylation: dynamic interplay with pre-mRNA splicing.

Davie, James R / Xu, Wayne / Delcuve, Genevieve P

Biochemistry and cell biology = Biochimie et biologie cellulaire

2016 Volume 94, Issue 1, Page(s) 1–11

Abstract: Histone H3 lysine 4 trimethylation (H3K4me3) is often stated as a mark of transcriptionally active promoters. However, closer study of the positioning of H3K4me3 shows the mark locating primarily after the first exon at the 5' splice site and overlapping ...

Abstract	Histone H3 lysine 4 trimethylation (H3K4me3) is often stated as a mark of transcriptionally active promoters. However, closer study of the positioning of H3K4me3 shows the mark locating primarily after the first exon at the 5' splice site and overlapping with a CpG island in mammalian cells. There are several enzyme complexes that are involved in the placement of the H3K4me3 mark, including multiple protein complexes containing SETD1A, SETD1B, and MLL1 enzymes (writers). CXXC1, which is associated with SETD1A and SETD1B, target these enzymes to unmethylated CpG islands. Lysine demethylases (KDM5 family members, erasers) demethylate H3K4me3. The H3K4me3 mark is recognized by several proteins (readers), including lysine acetyltransferase complexes, chromatin remodelers, and RNA bound proteins involved in pre-mRNA splicing. Interestingly, attenuation of H3K4me3 impacts pre-mRNA splicing, and inhibition of pre-mRNA splicing attenuates H3K4me3.
MeSH term(s)	Acetylation ; Animals ; CpG Islands ; Epigenesis, Genetic ; Exons ; Histone Acetyltransferases/metabolism ; Histone Code ; Histone Demethylases/metabolism ; Histone-Lysine N-Methyltransferase/metabolism ; Histones/chemistry ; Histones/genetics ; Humans ; Introns ; Lysine/chemistry ; Methylation ; Nucleosomes/chemistry ; Promoter Regions, Genetic ; RNA Precursors/chemistry ; RNA Splicing ; Transcription, Genetic
Chemical Substances	Histones ; Nucleosomes ; RNA Precursors ; Histone Demethylases (EC 1.14.11.-) ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43) ; Histone Acetyltransferases (EC 2.3.1.48) ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2016-02
Publishing country	Canada
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	54104-7
ISSN	1208-6002 ; 0829-8211
ISSN (online)	1208-6002
ISSN	0829-8211
DOI	10.1139/bcb-2015-0065
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: SARS‐CoV ‐2 multifaceted interaction with the human host. Part II

Beacon, Tasnim H. / Su, Ruey‐Chyi / Lakowski, Ted M. / Delcuve, Geneviève P. / Davie, James R.

IUBMB Life ; ISSN 1521-6543 1521-6551

Innate immunity response, immunopathology, and epigenetics

2020

Keywords	Clinical Biochemistry ; Genetics ; Cell Biology ; Biochemistry ; Molecular Biology ; covid19
Language	English
Publisher	Wiley
Publishing country	us
Document type	Article ; Online
DOI	10.1002/iub.2379
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SARS-CoV-2 multifaceted interaction with human host. Part I

Delcuve, Geneviève P. / Lakowski, Ted M. / Su, Ruey-Chyi / Beacon, Tasnim H. / Davie, James R.

IUBMB Life ; ISSN 1521-6543

What we have learnt and done so far, and the still unknown realities

2020

Keywords	Clinical Biochemistry ; Genetics ; Cell Biology ; Biochemistry ; Molecular Biology ; covid19
Language	English
Publisher	Wiley
Publishing country	us
Document type	Article ; Online
DOI	10.1002/iub.2380
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: SARS-CoV-2 multifaceted interaction with the human host. Part II: Innate immunity response, immunopathology, and epigenetics

Beacon, Tasnim H / Su, Ruey-Chyi / Lakowski, Ted M / Delcuve, Geneviève P / Davie, James R

IUBMB life

Abstract	The SARS-CoV-2 makes its way into the cell via the ACE2 receptor and the proteolytic action of TMPRSS2. In response to the SARS-CoV-2 infection, the innate immune response is the first line of defense, triggering multiple signaling pathways to produce interferons, pro-inflammatory cytokines and chemokines, and initiating the adaptive immune response against the virus. Unsurprisingly, the virus has developed strategies to evade detection, which can result in delayed, excessive activation of the innate immune system. The response elicited by the host depends on multiple factors, including health status, age, and sex. An overactive innate immune response can lead to a cytokine storm, inflammation, and vascular disruption, leading to the vast array of symptoms exhibited by COVID-19 patients. What is known about the expression and epigenetic regulation of the ACE2 gene and the various players in the host response are explored in this review.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #763131
Database	COVID19

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Article: SARS-CoV-2 multifaceted interaction with human host. Part I: What we have learnt and done so far, and the still unknown realities

Delcuve, Geneviève P / Lakowski, Ted M / Su, Ruey-Chyi / Beacon, Tasnim H / Davie, James R

IUBMB life

Abstract	SARS-CoV-2, the causing agent of the ongoing COVID-19 pandemic, is a beta-coronavirus which has 80% genetic homology with SARS-CoV, but displays increased virulence and transmissibility. Initially, SARS-CoV-2 was considered a respiratory virus generally causing a mild disease, only severe and fatal in the elderly and individuals with underlying conditions. Severe illnesses and fatalities were attributed to a cytokine storm, an excessive response from the host immune system. However, with the number of infections over 10 millions and still soaring, the insidious and stealthy nature of the virus has emerged, as it causes a vast array of diverse unexpected symptoms among infected individuals, including the young and healthy. It has become evident that besides infecting the respiratory tract, SARS-CoV-2 can affect many organs, possibly through the infection of the endothelium. This review presents an overview of our learning curve with the novel virus emergence, transmission, pathology, biological properties and host-interactions. It also briefly describes remedial measures taken until an effective vaccine is available, that is non-pharmaceutical interventions to reduce the viral spread and the repurposing of existing drugs, approved or in development for other conditions to eliminate the virus or mitigate the cytokine storm.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #754829
Database	COVID19

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