Human cytomegalovirus induces neuronal gene expression to promote virion maturation in macroH2A1-dependent manner
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ABSTRACT:
PROVIDER: PRJNA1231484 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32567615_1.fastq.gz | Fastqsanger.gz | |||
| SRR32567615_2.fastq.gz | Fastqsanger.gz | |||
| SRR32567616_1.fastq.gz | Fastqsanger.gz | |||
| SRR32567616_2.fastq.gz | Fastqsanger.gz | |||
| SRR32567617_1.fastq.gz | Fastqsanger.gz |
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Project description:Human cytomegalovirus (HCMV) uniquely remodels host cells, generating a cytoplasmic viral-induced assembly compartment (vIAC) and a kidney-bean-shaped nucleus. How these stark morphology changes take place in the context of host gene regulation is still emerging. Here, we discovered that HCMV titers, but not virus particle numbers, were significantly reduced in the absence of the histone variant macroH2A1, indicating that macroH2A1 is essential for producing infectious progeny. Because virion maturation and cellular remodeling are closely linked processes, we used confocal and electron microscopy to define structural changes in the host cell. We uncovered that HCMV-induced reorganization of the host nucleus, cytoskeleton, and endoplasmic reticulum does not occur in the absence of macroH2A1. Furthermore, we discovered using RNA-seq that while all viral genes were highly expressed in the absence of macroH2A1, many HCMV-induced host genes were not. Hundreds of these HCMV-induced macroH2A1-dependent host genes are associated with neuronal synapse formation and vesicle trafficking. Knock-down during infection of several HCMV-induced neuronal genes resulted in malformed vIACs and smaller plaques, establishing their importance to HCMV infection. Together, our findings demonstrate that HCMV manipulates host gene expression to hijack the dormant neuronal secretory pathway for proper virion maturation.
2025-06-16 | GSE291064 | GEO
Project description:Human cytomegalovirus (HCMV) uniquely remodels host cells, generating a cytoplasmic viral-induced assembly compartment (vIAC) and a kidney-bean-shaped nucleus. How these stark morphology changes take place in the context of host gene regulation is still emerging. Here, we discovered that HCMV titers, but not virus particle numbers, were significantly reduced in the absence of the histone variant macroH2A1, indicating that macroH2A1 is essential for producing infectious progeny. Because virion maturation and cellular remodeling are closely linked processes, we used confocal and electron microscopy to define structural changes in the host cell. We uncovered that HCMV-induced reorganization of the host nucleus, cytoskeleton, and endoplasmic reticulum does not occur in the absence of macroH2A1. Furthermore, we discovered using RNA-seq that while all viral genes were highly expressed in the absence of macroH2A1, many HCMV-induced host genes were not. Hundreds of these HCMV-induced macroH2A1-dependent host genes are associated with neuronal synapse formation and vesicle trafficking. Knock-down during infection of several HCMV-induced neuronal genes resulted in malformed vIACs and smaller plaques, establishing their importance to HCMV infection. Together, our findings demonstrate that HCMV manipulates host gene expression to hijack the dormant neuronal secretory pathway for proper virion maturation.
2025-06-16 | GSE272267 | GEO
Project description:Human Cytomegalovirus (HCMV) infects over 50% of humans, is a leading cause of congenital birth defects, and poses serious risks for immuno-compromised individuals. To expand the molecular knowledge governing virion assembly and egress, we initiated a proteomics-based investigation and identified a significant proportion of host exosome constituents in HCMV virions. Quantitative analysis of exosomes released from uninfected cells (765 proteins) revealed that over 99% of the protein cargo was subsequently integrated into virions, confirming near-complete acquisition of exosome biogenesis during infection. We confirmed VAMP3 is essential for viral trafficking and release of infectious progeny, further validating the intrinsic exploitation of the pathway by HCMV. Therefore, host exosomes serve as the molecular template for virion cargo addition, and provide an export mechanism for virion egress. Our discovery underpins future investigation of host exosome proteins as important modulators of viral maturation, and enhances the understanding of HCMV envelopment, trafficking, fusion and release.
2021-02-22 | PXD015081 | Pride
Project description:The assembly of human cytomegalovirus (HCMV) virions is an orchestrated process that requires, as an essential prerequisite, the complex crosstalk between viral structural proteins. So far, however, the mechanisms governing the successive steps in the constitution of virion protein complexes remained elusive. Protein phosphorylation is a key regulator determining the sequential changes in conformation, binding, dynamics and stability of proteins in the course of multiprotein assembly. Here, we present new results to complete knowledge on HCMV virion proteome and phosphoproteome. Thus, a novel dataset of viral and cellular proteins contained in HCMV virions has been generated, providing a basis for future analyses of individual phosphorylation steps and sites involved in the orchestrated assembly of HCMV virion-specific multiprotein complexes.
2020-06-05 | PXD012921 | Pride
Project description:Human cytomegalovirusinduces neuronal geneexpression to promote virionmaturationin macroH2A1-dependent manner
| PRJNA1135976 | ENA
Project description:MacroH2A1 is a histone variant that is enriched on the inactive X chromosome (Xi) in mammals and is postulated to play an important, but unknown, role in the repression of gene expression. Here we show that although macroH2A1 marks repressed autosomal chromatin, it positively regulates transcription when located in the transcribed regions of many target genes. We used chromatin immunoprecipitation coupled with tiling microarrays (ChIP-chip) to determine the genomic localization of macroH2A1 in IMR90 human primary lung fibroblasts and MCF-7 breast cancer cells. The patterns of macroH2A1 deposition are largely similar across the autosomes of both cell lines. Our studies revealed a genomic localization pattern unique among histone variants, namely the occupation by macroH2A1 of large chromatin domains (>500 kb in some cases) that contain repressive chromatin marks (e.g., histone H3 lysine 27 trimethylation). The boundaries of macroH2A1-containing domains tend to occur in promoter proximal regions. Not all promoters, however, serve as macroH2A1 boundaries; many macroH2A1-containing chromatin domains invade the transcribed regions of genes whose products play key roles in development and cell-cell signaling. Surprisingly, the expression of many of these genes is positively regulated by macroH2A1. MacroH2A1 also plays a role in augmenting signal-regulated transcription, specifically for genes responsive to serum starvation. Collectively, our results document an unexpected role for macroH2A1 in the escape from heterochromatin-associated silencing and the enhancement of autosomal gene transcription. Two macroH2A1 ChIP-chip biological replicates from IMR90 human embryonic lung fibroblasts are included.
2010-06-20 | E-GEOD-18633 | biostudies-arrayexpress
Project description:MacroH2A1 is a histone variant that is enriched on the inactive X chromosome (Xi) in mammals and is postulated to play an important, but unknown, role in the repression of gene expression. Here we show that although macroH2A1 marks repressed autosomal chromatin, it positively regulates transcription when located in the transcribed regions of many target genes. We used chromatin immunoprecipitation coupled with tiling microarrays (ChIP-chip) to determine the genomic localization of macroH2A1 in IMR90 human primary lung fibroblasts and MCF-7 breast cancer cells. The patterns of macroH2A1 deposition are largely similar across the autosomes of both cell lines. Our studies revealed a genomic localization pattern unique among histone variants, namely the occupation by macroH2A1 of large chromatin domains (>500 kb in some cases) that contain repressive chromatin marks (e.g., histone H3 lysine 27 trimethylation). The boundaries of macroH2A1-containing domains tend to occur in promoter proximal regions. Not all promoters, however, serve as macroH2A1 boundaries; many macroH2A1-containing chromatin domains invade the transcribed regions of genes whose products play key roles in development and cell-cell signaling. Surprisingly, the expression of many of these genes is positively regulated by macroH2A1. MacroH2A1 also plays a role in augmenting signal-regulated transcription, specifically for genes responsive to serum starvation. Collectively, our results document an unexpected role for macroH2A1 in the escape from heterochromatin-associated silencing and the enhancement of autosomal gene transcription.
2009-11-13 | GSE18633 | GEO
Project description:We produced a genome-wide map of the distribution of macroH2A1 histone variants in mouse liver chromatin using high-throughput sequencing of DNA from macroH2A1 nucleosomes. Although macroH2A1 nucleosomes are widely distributed across the genome, their local concentration varies over a range of 100-fold or more. The transcribed regions of most active genes are depleted of macroH2A1, with many showing depletion of 3-fold or more. The inactive X chromosome appears to have relatively uniform macroH2A1 enrichment that averages approximately 3.9-fold, but most genes that are known to escape from X inactivation do not show this enrichment. We used macroH2A1 depletion to identify additional genes that escape X inactivation, but overall, our map supports the idea that relatively few genes escape in the mouse. The map also helped identify genes that appear to be direct targets of macroH2A1-mediated repression.
2010-11-10 | GSE18963 | GEO
Project description:The histone variant macroH2A1 and the poly(ADP-ribose) polymerase PARP-1 both regulate gene transcription by modulating chromatin structure and function. Of the two macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, the former is often suppressed in cancer and has the unique ability to interact with poly(ADP-ribose). Using ChIP-seq in primary lung fibroblasts, we demonstrate that macroH2A1 is incorporated into either of two spatially and functionally distinct types of chromatin; the first is marked by H3 K27 trimethylation, while the second contains a set of nine histone acetylations. MacroH2A1-regulated genes are involved in cancer progression are specifically found in macroH2A1-containing acetylated chromatin. Through the recruitment of PARP-1, macroH2A1.1 promotes the acetylation of H2B K12 and K120 which plays a key role in the regulation of macroH2A1 target genes in primary cells. The macroH2A1/PARP-1 pathway regulating H2B K12 and K120 acetylation is disrupted in cancer cells, in part, explaining macroH2A1’s role in cancer suppression.
2014-09-15 | GSE54845 | GEO
Project description:The histone variant macroH2A1 and the poly(ADP-ribose) polymerase PARP-1 both regulate gene transcription by modulating chromatin structure and function. Of the two macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, the former is often suppressed in cancer and has the unique ability to interact with poly(ADP-ribose). Using ChIP-seq in primary lung fibroblasts, we demonstrate that macroH2A1 is incorporated into either of two spatially and functionally distinct types of chromatin; the first is marked by H3 K27 trimethylation, while the second contains a set of nine histone acetylations. MacroH2A1-regulated genes are involved in cancer progression are specifically found in macroH2A1-containing acetylated chromatin. Through the recruitment of PARP-1, macroH2A1.1 promotes the acetylation of H2B K12 and K120 which plays a key role in the regulation of macroH2A1 target genes in primary cells. The macroH2A1/PARP-1 pathway regulating H2B K12 and K120 acetylation is disrupted in cancer cells, in part, explaining macroH2A1M-bM-^@M-^Ys role in cancer suppression. Two biological replicates of the macroH2A1 ChIP and two corresponding input samples were sequenced
2014-09-15 | E-GEOD-54845 | biostudies-arrayexpress