Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human cytomegalovirus IE2 drives transcription initiation from a select subset of late infection viral promoters by host RNA polymerase II

ABSTRACT: Human cytomegalovirus IE2 drives transcription initiation from a select subset of late infection viral promoters by host RNA polymerase II

PROVIDER: PRJNA578406 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR10312745_1.fastq.gz	Fastqsanger.gz
	SRR10312745_2.fastq.gz	Fastqsanger.gz
	SRR10312746_1.fastq.gz	Fastqsanger.gz
	SRR10312746_2.fastq.gz	Fastqsanger.gz
	SRR10312747_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 44

Similar Datasets

Human cytomegalovirus IE2 drives transcription initiation from a select subset of late infection viral promoters by host RNA polymerase II

Project description:Herpesvirus late promoters activate gene expression after viral DNA synthesis has begun. Alphaherpesviruses utilize a viral immediate-early protein to do this, whereas beta- and gammaherpesviruses primarily use a 6-member set of viral late-acting transcription factors (LTF) that are drawn to a TATT sequence in the late promoter. The betaherpesvirus, human cytomegalovirus (HCMV), produces three immediate-early 2 protein isoforms, IE2-86, IE2-60, IE2-40, in late infection, but whether they activate late viral promoters is unknown. Here, we quickly degrade the IE2 proteins in late infection and analyze effects on transcription using customized PRO-Seq and computational methods combined with multiple validation methods. We discover that the IE2 proteins selectively drive RNA Pol II transcription initiation at a subset of viral early-late and late promoters common to different HCMV strains, but do not substantially affect Pol II transcription of the 9,942 expressed host genes. Most of the IE2-activated viral late infection promoters lack the TATT sequence bound by the HCMV UL87-encoded LTF. The HCMV TATT-binding protein is not mechanistically involved in late RNA expression from the IE2-activated TATT-less UL83 (pp65) promoter, as it is for the TATT-containing UL82 (pp71) promoter. While antecedent viral DNA synthesis is necessary for transcription from the late infection viral promoters, continued viral DNA synthesis is unnecessary. We conclude that the IE2 proteins target a distinct subset of late infection HCMV promoters for transcription initiation by RNA Pol II. Commencement of viral DNA replication renders the HCMV genome late promoters susceptible to late-acting viral transcription factors, which do not appreciably affect host transcription during this late time.

2020-03-05 | GSE139114 | GEO

Human cytomegalovirus IE2 drives transcription initiation from a select subset of late infection viral promoters by host RNA polymerase II.

Project description:Herpesvirus late promoters activate gene expression after viral DNA synthesis has begun. Alphaherpesviruses utilize a viral immediate-early protein to do this, whereas beta- and gammaherpesviruses primarily use a 6-member set of viral late-acting transcription factors (LTF) that are drawn to a TATT sequence in the late promoter. The betaherpesvirus, human cytomegalovirus (HCMV), produces three immediate-early 2 protein isoforms, IE2-86, IE2-60, IE2-40, late in infection, but whether they activate late viral promoters is unknown. Here, we quickly degrade the IE2 proteins in late infection using dTag methodology and analyze effects on transcription using customized PRO-Seq and computational methods combined with multiple validation methods. We discover that the IE2 proteins selectively drive RNA Pol II transcription initiation at a subset of viral early-late and late promoters common to different HCMV strains, but do not substantially affect Pol II transcription of the 9,942 expressed host genes. Most of the IE2-activated viral late infection promoters lack the TATT sequence bound by the HCMV UL87-encoded LTF. The HCMV TATT-binding protein is not mechanistically involved in late RNA expression from the IE2-activated TATT-less UL83 (pp65) promoter, as it is for the TATT-containing UL82 (pp71) promoter. While antecedent viral DNA synthesis is necessary for transcription from the late infection viral promoters, continued viral DNA synthesis is unnecessary. We conclude that in late infection the IE2 proteins target a distinct subset of HCMV early-late and late promoters for transcription initiation by RNA Pol II. Commencement of viral DNA replication renders the HCMV genome late promoters susceptible to late-acting viral transcription factors.

| S-EPMC7162547 | biostudies-literature

Human cytomegalovirus IE2 both activates and represses initiation and modulates elongation in a context-dependent manner

Project description:Using PRO-Seq, which profiles nascent transcripts, and a recently developed DFF-ChIP approach that informs on local chromatin environment, we show that IE2 controls viral gene transcription in three distinct capacities during late HCMV infection and reveal mechanisms involving direct binding of IE2 to viral DNA. IE2 represses a subset of viral promoters by binding within the target core promoter region, blocking the assembly preinitiation complexes (PICs). Remarkably, IE2 forms a repressive complex at the major immediate-early promoter region involving direct association of IE2 with nucleosomes and TBP. IE2 activates transcription by binding proximal to, but not within, core promoter regions. In addition, evidence is provided that IE2 functions as a direct roadblock to transcription elongation. At one locus, this function of IE2 is demonstrated to be important for the synthesis of a spliced RNA. Consistent with the minimal observed effects of IE2 depletion on host gene transcription, IE2 only sparingly engages the host genome.

2022-05-11 | GSE193026 | GEO

miRNA-mediated targeting of human cytomegalovirus reveals biological host and viral targets of IE2

Project description:We introduce target sites for the microRNA (miRNA) miR-142 into the 3’-untranslated region of the human cytomegalovirus (HCMV) IE2 to study the transcriptional effect of IE2 knock-down on both viral and host genes in cells that express miR-142. When comparing transcriptional data from miR-142 expressing macrophages infected with HCMV to macrophages infected with IE2-miR-142 targeted HCMV, we see a knock-down of IE2 and differential regulation of predicted viral targets of IE2 including IE1, vIL-10 and US29. We then generated fibroblasts expressing miR-142 to study the knock-down of IE2 in a different cellular system and find drastic differences in loss of IE2 on the host transcriptional profile in the two different cell types.

2017-12-28 | GSE107680 | GEO

Human cytomegalovirus IE2 both activates and represses initiation and modulates elongation in a context-dependent manner

Project description:Human cytomegalovirus IE2 both activates and represses initiation and modulates elongation in a context-dependent manner

| PRJNA794151 | ENA

Late-rising CD4 T cells resolve cytomegalovirus persistent replication

Project description:Conventional antiviral memory CD4 T cells typically arise during the first two weeks of acute infection. Unlike most viruses, cytomegalovirus (CMV) exhibits an extended persistent replication phase followed by lifelong latency accompanied with some gene expression, suggesting the development of protective memory CD4 T cells may be altered. We show that during mouse CMV (MCMV) infection, CD4 T cells recognizing an epitope derived from the viral M09 protein only develop after conventional memory T cells have already peaked and contracted. Ablating these CD4 T cells by mutating the M09 genomic epitope in the MCMV Smith strain, or inducing them by introducing the epitope into the K181 strain, resulted in delayed or enhanced control of viral persistence, respectively. These cells were shown to be unique compared to their conventional memory counterparts; producing higher IFNg and IL-2 and lower IL-10 levels. RNAseq analyses revealed them to express distinct subsets of effector genes as compared to classical CD4 T cells. Additionally, when M09 cells were induced by epitope vaccination they significantly enhanced protection when compared to conventional CD4 T cells alone. These data show that late-rising CD4 T cells are a unique memory subset with excellent protective capacities that display a development program strongly differing from the majority of memory T cells.

2023-11-30 | GSE237946 | GEO

Decoding murine cytomegalovirus

Project description:Decoding murine cytomegalovirus

| PRJNA874807 | ENA

miRNA-mediated targeting of human cytomegalovirus reveals biological host and viral targets of IE2

Project description:miRNA-mediated targeting of human cytomegalovirus reveals biological host and viral targets of IE2

| PRJNA421010 | ENA

Cytomegalovirus Late Transcription Factor Target Sequence Diversity Orchestrates Viral Early to Late Transcription

Project description:Herpesviruses have a group of genes earmarked for expression late in the infection. Beta- and gammaherpesviruses utilize a six-member set of viral late transcription factors to selectively activate these genes by binding to a DNA sequence signature in gene promoters. We made an unexpected discovery that differences in sequence signature configures the late gene expression program for human cytomegalovirus, a beta-herpesvirus of global public health importance. Diversity in signature patterns expands promoter targets and pre-sets amount of individual promoter output. A unique palindromic sequence signature is linked to the activation of back-to-back promoters at multiple locations in the viral genome. We deduce that diversity in late transcription factor targets functionally orchestrates the productive rollout of the late-stage infection. This may be a generalizable feature adopted by beta- and gammaherpesvirus subfamilies.

2021-07-01 | GSE168165 | GEO

Late-rising CD4 T cells resolve cytomegalovirus persistent replication

Project description:Late-rising CD4 T cells resolve cytomegalovirus persistent replication

| PRJNA997285 | ENA