Genomic landscape of transcriptionally active histone arginine methylation marks, H3R2me2s and H4R3me2a, relative to nucleosome depleted regions

Beacon, Tasnim H.; Xu, Wayne; Davie, James R.

doi:10.1016/j.gene.2020.144593

Cited by 27 publications

(29 citation statements)

References 46 publications

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“…Second, H3K27ac, while a typical modification that regulates genomic function, can only provide relatively limited information about transcriptional activity (Kimura, 2013;Nammo et al, 2018). We found the differences in a number of genes annotated to differentially acetylated peaks and revealed their associated signaling pathways, supporting the notion that dysregulation of H3K27 acetylation and the PPAR signaling pathway are involved in the excessive accumulation of fat in liver tissue and the onset of lipid metabolic disorders (Chinetti et al, 2000;Beacon et al, 2020). Nevertheless, further experiments are still required to confirm the model and candidate genes.…”

Section: Discussionsupporting

confidence: 66%

Dysregulated H3K27 Acetylation Is Implicated in Fatty Liver Hemorrhagic Syndrome in Chickens

Zhu

Zeng

et al. 2021

Front. Genet.

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Epigenetic regulation of gene expression has been reported in the pathogenesis of metabolic disorders such as diabetes and liver steatosis in humans. However, the molecular mechanisms of fatty liver hemorrhagic syndrome (FLHS) in chickens have been rarely studied. H3K27ac chromatin immunoprecipitation coupled with high-throughput sequencing and high-throughput RNA sequencing was performed to compare genome-wide H3K27ac profiles and transcriptomes of liver tissue between healthy and FLHS chickens. In total, 1,321 differential H3K27ac regions and 443 differentially expressed genes were identified (| log2Fold change| ≥ 1 and P-value ≤ 0.05) between the two groups. Binding motifs for transcription factors involved in immune processes and metabolic homeostasis were enriched among those differential H3K27ac regions. Differential H3K27ac peaks were associated with multiple known FLHS risk genes, involved in lipid and energy metabolism (PCK1, APOA1, ANGPTL4, and FABP1) and the immune system (FGF7, PDGFRA, and KIT). Previous studies and our current results suggested that the high-energy, low-protein (HELP) diet might have an impact on histone modification and chromatin structure, leading to the dysregulation of candidate genes and the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which causes excessive accumulation of fat in the liver tissue and induces the development of FLHS. These findings highlight that epigenetic modifications contribute to the regulation of gene expression and play a central regulatory role in FLHS. The PPAR signaling pathway and other genes implicated in FLHS are of great importance for the development of novel and specific therapies for FLHS-susceptible commercial laying hens.

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Section: Discussionsupporting

confidence: 66%

Dysregulated H3K27 Acetylation Is Implicated in Fatty Liver Hemorrhagic Syndrome in Chickens

Zhu

Zeng

et al. 2021

Front. Genet.

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“…2 B). In chicken erythroid cells, genes [e.g., IRF7 , FTH1 , HBBA (β-globin), HBA1 (α-globin)] have the broad epigenetic domain [ 47 ] (Fig. 3 ).…”

Section: Breadth Of the Broad Epigenetic Domain As A Key Chromatin Signaturementioning

confidence: 99%

The dynamic broad epigenetic (H3K4me3, H3K27ac) domain as a mark of essential genes

et al. 2021

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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.

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“…[152][153][154][155] Further, protein arginine methyltransferases (PRMT) play critical roles in establishing active marks. 156,157 PRMT1, which catalyzes the formation of H4 asymmetrically dimethylated at arginine 3 (H4R3me2a), is important in enhancer-promoter interactions. 157 The mitogen-activated protein kinase (MAPK) and AKT pathways are activated in cells infected with coronaviruses.…”

Section: Epigenetic Basicsmentioning

confidence: 99%

“…156,157 PRMT1, which catalyzes the formation of H4 asymmetrically dimethylated at arginine 3 (H4R3me2a), is important in enhancer-promoter interactions. 157 The mitogen-activated protein kinase (MAPK) and AKT pathways are activated in cells infected with coronaviruses. 158,159 Among the MAPK pathways are the extracellular signal-regulated kinase (ERK), p38 MAPK, and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK).…”

Section: Epigenetic Basicsmentioning

confidence: 99%

“…KATs and HDACs are important regulators of inflammatory gene expression 152–155 . Further, protein arginine methyltransferases (PRMT) play critical roles in establishing active marks 156,157 . PRMT1, which catalyzes the formation of H4 asymmetrically dimethylated at arginine 3 (H4R3me2a), is important in enhancer‐promoter interactions 157 …”

Section: Epigenetics Innate Immunity Response and Inflammationmentioning

confidence: 99%

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

Beacon

Su²,

Lakowski

et al. 2020

IUBMB Life

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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.

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Genomic landscape of transcriptionally active histone arginine methylation marks, H3R2me2s and H4R3me2a, relative to nucleosome depleted regions

Cited by 27 publications

References 46 publications

Dysregulated H3K27 Acetylation Is Implicated in Fatty Liver Hemorrhagic Syndrome in Chickens

Dysregulated H3K27 Acetylation Is Implicated in Fatty Liver Hemorrhagic Syndrome in Chickens

The dynamic broad epigenetic (H3K4me3, H3K27ac) domain as a mark of essential genes

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

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