Changes in H3K27ac following lipopolysaccharide stimulation of nasopharyngeal epithelial cells

Borghini, Lisa; Hibberd, Martin L.; Dávila, Sonia

doi:10.1186/s12864-018-5295-4

Cited by 7 publications

(5 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Enrichment level of both H3K27ac and H3K4me3 increased 2h after LPS or Poly (I:C), and then decreased at 6h. In summary, a high number of DHMRs in AM after LPS or Poly (I:C) stimulation were detected, with the H3K27ac as the most dynamic histone mark, as reported by others ( Novakovic et al, 2016 ; Borghini et al, 2018 ; Daskalaki et al, 2018 ), followed by H3K4me3.…”

Section: Resultssupporting

confidence: 77%

“…This change in the chromatin state was consistent with the increased expression of TNF at 2h after both LPS and Poly (I:C) stimulations and decreased expression at 6h LPS treatment and return to baseline for the 6h Poly (I:C) treatment. A similar pattern of H3K27ac modification near the promoter region of TNF have been observed in human nasopharyngeal epithelial cells in response to LPS: enrichment of binding sites of RELA and AP-1 members in H3K27ac peak regions in non-stimulated cells; and the increase of HM enrichment in the promoter region after LPS treatment, all contributing to the induction of the early response gene TNF (Borghini et al, 2018). In addition to the permissive chromatin for the immediate inflammatory response, we were able to identify an upregulated TF NRF2, which was associated with the increase of the H3K27ac motif enrichment in LPS and Poly(I:C) treatment.…”

Section: Discussionsupporting

confidence: 68%

See 1 more Smart Citation

Changes in H3K27ac at Gene Regulatory Regions in Porcine Alveolar Macrophages Following LPS or PolyIC Exposure

Herrera-Uribe

Byrne

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

Changes in chromatin structure, especially in histone modifications (HMs), linked with chromatin accessibility for transcription machinery, are considered to play significant roles in transcriptional regulation. Alveolar macrophages (AM) are important immune cells for protection against pulmonary pathogens, and must readily respond to bacteria and viruses that enter the airways. Mechanism(s) controlling AM innate response to different pathogen-associated molecular patterns (PAMPs) are not well defined in pigs. By combining RNA sequencing (RNA-seq) with chromatin immunoprecipitation and sequencing (ChIP-seq) for four histone marks (H3K4me3, H3K4me1, H3K27ac and H3K27me3), we established a chromatin state map for AM stimulated with two different PAMPs, lipopolysaccharide (LPS) and Poly(I:C), and investigated the potential effect of identified histone modifications on transcription factor binding motif (TFBM) prediction and RNA abundance changes in these AM. The integrative analysis suggests that the differential gene expression between non-stimulated and stimulated AM is significantly associated with changes in the H3K27ac level at active regulatory regions. Although global changes in chromatin states were minor after stimulation, we detected chromatin state changes for differentially expressed genes involved in the TLR4, TLR3 and RIG-I signaling pathways. We found that regions marked by H3K27ac genomewide were enriched for TFBMs of TF that are involved in the inflammatory response. We further documented that TF whose expression was induced by these stimuli had TFBMs enriched within H3K27ac-marked regions whose chromatin state changed by these same stimuli. Given that the dramatic transcriptomic changes and minor chromatin state changes occurred in response to both stimuli, we conclude that regulatory elements (i.e. active promoters) that contain transcription factor binding motifs were already active/poised in AM for immediate inflammatory response to PAMPs. In summary, our data provides the first chromatin state map of porcine AM in response to bacterial and viral PAMPs, contributing to the Functional Annotation of Animal Genomes (FAANG) project, and demonstrates the role of HMs, especially H3K27ac, in regulating transcription in AM in response to LPS and Poly(I:C).

show abstract

Section: Resultssupporting

confidence: 77%

Section: Discussionsupporting

confidence: 68%

Changes in H3K27ac at Gene Regulatory Regions in Porcine Alveolar Macrophages Following LPS or PolyIC Exposure

Herrera-Uribe

Byrne

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…are current employees and shareholders of GSK Plc. Data and materials availability: All data contained in this paper are publicly available and referenced in Table S6 , together with all gene expression omnibus numbers for access: GSE147507 ( 13 ), GSE150316 ( 56 ), HRA000143 ( 57 ), GSE150819, GSE98372 ( 25 ), GSE145926 ( 58 ), GSE122960 ( 59 ), GSE150728 ( 55 ), GSE132018 ( 60 ), ENCODE (ENCFF137KNW; ENCFF055YQO; ENCFF677KZQ;ENCFF000XLN), PXD020019 ( 61 ). All (other) data needed to evaluate the conclusions in the paper are present in the paper or the Supplementary Materials.…”

Section: Acknowledgmentsmentioning

confidence: 99%

SARS-CoV-2 drives JAK1/2-dependent local complement hyperactivation

et al. 2021

View full text Add to dashboard Cite

Patients with coronavirus disease 2019 (COVID-19) present a wide range of acute clinical manifestations affecting the lungs, liver, kidneys and gut. Angiotensin converting enzyme (ACE) 2, the best-characterized entry receptor for the disease-causing virus SARS-CoV-2, is highly expressed in the aforementioned tissues. However, the pathways that underlie the disease are still poorly understood. Here, we unexpectedly found that the complement system was one of the intracellular pathways most highly induced by SARS-CoV-2 infection in lung epithelial cells. Infection of respiratory epithelial cells with SARS-CoV-2 generated activated complement component C3a and could be blocked by a cell-permeable inhibitor of complement factor B (CFBi), indicating the presence of an inducible cell-intrinsic C3 convertase in respiratory epithelial cells. Within cells of the bronchoalveolar lavage of patients, distinct signatures of complement activation in myeloid, lymphoid and epithelial cells tracked with disease severity. Genes induced by SARS-CoV-2 and the drugs that could normalize these genes both implicated the interferon-JAK1/2-STAT1 signaling system and NF-κB as the main drivers of their expression. Ruxolitinib, a JAK1/2 inhibitor, normalized interferon signature genes and all complement gene transcripts induced by SARS-CoV-2 in lung epithelial cell lines, but did not affect NF-κB-regulated genes. Ruxolitinib, alone or in combination with the antiviral remdesivir, inhibited C3a protein produced by infected cells. Together, we postulate that combination therapy with JAK inhibitors and drugs that normalize NF-κB-signaling could potentially have clinical application for severe COVID-19.

show abstract

“…Further studies are required to better understand molecular mechanisms involved in NPC pathophysiology, such as the roles of lipopolysaccharide (LPS) and general inflammation on nasopharyngeal tissue injury, HOXA10 and matrix metalloproteinases 1 and 3 (MMP1, MMP3) pathways. LPS is a bacterial endotoxin on gram negative bacteria and makes contact with the nasopharynx through normal airflow and eating that can lead to the induction of numerous pathological pathways associated with immune defense [25,26]. As such, it has been hypothesized that LPS could be a leading driver and inducer of tumorigenesis of NPC, possibly through inflammation [26].…”

Section: Introductionmentioning

confidence: 99%

Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis

et al. 2021

View full text Add to dashboard Cite

Background Nasopharyngeal carcinoma (NPC) is a cancer of epithelial origin with a high incidence in certain populations. While NPC has a high remission rate with concomitant chemoradiation, recurrences are frequent, and the downstream morbidity of treatment is significant. Thus, it is imperative to find alternative therapies. Methods We employed a Search Tag Analyze Resource (STARGEO) platform to conduct a meta-analysis using the National Center for Biotechnology’s (NCBI) Gene Expression Omnibus (GEO) to define NPC pathogenesis. We identified 111 tumor samples and 43 healthy nasopharyngeal epithelium samples from NPC public patient data. We analyzed associated signatures in Ingenuity Pathway Analysis (IPA), restricting genes that showed statistical significance (p<0.05) and an absolute experimental log ratio greater than 0.15 between disease and control samples. Results Our meta-analysis identified activation of lipopolysaccharide (LPS)-induced tissue injury in NPC tissue. Additionally, interleukin-1 (IL-1) and SB203580 were the top upstream regulators. Tumorigenesis-related genes such as homeobox A10 (HOXA10) and prostaglandin-endoperoxide synthase 2 (PTGS2 or COX-2) as well as those associated with extracellular matrix degradation, such as matrix metalloproteinases 1 and 3 (MMP-1, MMP-3) were also upregulated. Decreased expression of genes that encode proteins associated with maintaining healthy nasal respiratory epithelium structural integrity, including sentan-cilia apical structure protein (SNTN) and lactotransferrin (LTF) was documented. Importantly, we found that etanercept inhibits targets upregulated in NPC and LPS induction, such as MMP-1, PTGS2, and possibly MMP-3. Conclusions Our analysis illustrates that nasal epithelial barrier dysregulation and maladaptive immune responses are key components of NPC pathogenesis along with LPS-induced tissue damage.

show abstract

Changes in H3K27ac following lipopolysaccharide stimulation of nasopharyngeal epithelial cells

Cited by 7 publications

References 37 publications

Changes in H3K27ac at Gene Regulatory Regions in Porcine Alveolar Macrophages Following LPS or PolyIC Exposure

Changes in H3K27ac at Gene Regulatory Regions in Porcine Alveolar Macrophages Following LPS or PolyIC Exposure

SARS-CoV-2 drives JAK1/2-dependent local complement hyperactivation

Meta-Analysis illustrates possible role of lipopolysaccharide (LPS)-induced tissue injury in nasopharyngeal carcinoma (NPC) pathogenesis

Contact Info

Product

Resources

About