scholarly journals The Histone Chaperone Anti-Silencing Function 1 Is a Global Regulator of Transcription Independent of Passage through S Phase

2005 ◽  
Vol 25 (2) ◽  
pp. 652-660 ◽  
Author(s):  
Susan R. Zabaronick ◽  
Jessica K. Tyler
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Transcriptional Repression ◽  
De Novo ◽  
S Phase ◽  
Global Changes ◽  
Histone Chaperones ◽  
Direct Role ◽  
Broad Array ◽  
Assembly Factor

ABSTRACT We investigated the function of the histone H3/H4 chaperones anti-silencing function 1 (Asf1p) and chromatin assembly factor 1 (CAF-1) in global transcriptional regulation in budding yeast. Deletion of ASF1 or CAF-1 components led to global transcriptional misregulation, both activation and repression, of genes scattered throughout the 16 yeast chromosomes. To investigate direct effects on gene regulation, we developed an approach to destabilize Asf1p that results in its rapid degradation within minutes of transcriptional repression. Upon degradation of Asf1p, rapid global changes in gene expression occur without the requirement for passage through S phase or de novo protein synthesis. In particular, we demonstrate that the previously reported influence of Asf1p on histone gene expression is not a direct effect of loss of Asf1p. These data indicate that the histone chaperones CAF-1 and Asf1p regulate the gene expression of a broad array of genes in yeast and, in the case of Asf1p, this is likely to be due to a direct role in chromatin modulation during transcriptional regulation.

scholarly journals Interaction of 7SK with the Smn complex modulates snRNP production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Changhe Ji ◽  
Jakob Bader ◽  
Pradhipa Ramanathan ◽  
Luisa Hennlein ◽  
Felix Meissner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Fine Tuning ◽  
Global Changes ◽  
Functional Association ◽  
Transcriptional Inhibition ◽  
Smn Complex ◽  
Core Components

AbstractGene expression requires tight coordination of the molecular machineries that mediate transcription and splicing. While the interplay between transcription kinetics and spliceosome fidelity has been investigated before, less is known about mechanisms regulating the assembly of the spliceosomal machinery in response to transcription changes. Here, we report an association of the Smn complex, which mediates spliceosomal snRNP biogenesis, with the 7SK complex involved in transcriptional regulation. We found that Smn interacts with the 7SK core components Larp7 and Mepce and specifically associates with 7SK subcomplexes containing hnRNP R. The association between Smn and 7SK complexes is enhanced upon transcriptional inhibition leading to reduced production of snRNPs. Taken together, our findings reveal a functional association of Smn and 7SK complexes that is governed by global changes in transcription. Thus, in addition to its canonical nuclear role in transcriptional regulation, 7SK has cytosolic functions in fine-tuning spliceosome production according to transcriptional demand.

Glucocorticoids inhibit IL-1β-induced GM-CSF expression at multiple levels: roles for the ERK pathway and repression by MKP-1

2010 ◽  
Vol 427 (1) ◽  
pp. 113-124 ◽  
Author(s):  
Robert Newton ◽  
Elizabeth M. King ◽  
Wei Gong ◽  
Christopher F. Rider ◽  
Karl J. Staples ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Transcriptional Repression ◽  
Actinomycin D ◽  
De Novo ◽  
A549 Cells ◽  
Mitogen Activated Protein Kinase ◽  
Erk Pathway ◽  
Gm Csf ◽  
Erk Phosphorylation

In the present study, IL (interleukin)-1β increased GM-CSF (granulocyte/macrophage colony-stimulating factor) expression from pulmonary A549 cells and primary HBE (human bronchial epithelial) cells. These responses were repressed by the glucocorticoid dexamethasone, allowing the use of A549 cells as a relevant model. IL-1β induced GM-CSF release into the culture medium by 6 h and in cell lysates (cytosolic) at 2 h. These effects were profoundly inhibited by dexamethasone, yet IL-1β-induced GM-CSF mRNA and unspliced nRNA (nuclear RNA; a surrogate of transcription rate) were modestly inhibited by dexamethasone at times up to 2 h. Although this indicates an effect on protein synthesis, actinomycin D chase experiments also indicated post-transcriptional repression by dexamethasone. Dexamethasone-dependent mRNA repression increased with time and was prevented by translational blockade. In addition, dexamethasone and the dissociated steroid RU24858 repressed GM-CSF release in an actinomycin D-sensitive manner, thereby implicating glucocorticoid-induced gene expression. At 2 h, IL-1β-induced expression of GM-CSF protein, but not mRNA, was sensitive to the MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase] inhibitors PD098059 and U0126. Although this indicates a role for the MEK/ERK pathway in GM-CSF translation, PD098059 subsequently destabilized GM-CSF mRNA. Dexamethasone and RU24858 both reduced IL-1β-induced ERK phosphorylation and increased MKP-1 (MAPK phosphatase-1) expression. Inhibition of ERK phosphorylation was reproduced by MKP-1 overexpression and prevented by MKP-1-targeting siRNA (small interfering RNA). Since MKP-1 prevented GM-CSF expression by transcriptional, post-transcriptional and translational processes, we propose that glucocorticoids induce MKP-1 expression to reduce both MEK/ERK activation and GM-CSF protein synthesis. Thus de novo gene expression, particularly of MKP-1, is involved in the repressive effects of glucocorticoids.

scholarly journals A novel plant-fungal association reveals fundamental sRNA and gene expression reprogramming at the onset of symbiosis

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ena Šečić ◽  
Silvia Zanini ◽  
Daniel Wibberg ◽  
Lukas Jelonek ◽  
Tobias Busche ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nutrient Uptake ◽  
Stress Responses ◽  
Growth And Development ◽  
De Novo ◽  
Brachypodium Distachyon ◽  
Defense Responses ◽  
Grass Species ◽  
Global Changes ◽  
Plant Metabolites

Abstract Background Beneficial associations between plants and microbes are widespread in nature and have been studied extensively in the microbial-dominant environment of the rhizosphere. Such associations are highly advantageous for the organisms involved, benefiting soil microbes by providing them access to plant metabolites, while plant growth and development are enhanced through the promotion of nutrient uptake and/or protection against (a)biotic stresses. While the establishment and maintenance of mutualistic associations have been shown to require genetic and epigenetic reprogramming, as well as an exchange of effector molecules between microbes and plants, whether short RNAs are able to effect such changes is currently unknown. Here, we established an interaction between the model grass species Brachypodium distachyon (Bd, Pooideae) and the beneficial fungal root endophyte Serendipita indica (Si, syn. Piriformospora indica, Sebacinales) to elucidate RNA interference-based regulatory changes in gene expression and small (s)RNA profiles that occurred during establishment of a Sebacinalean symbiosis. Results Colonization of Bd roots with Si resulted in higher grain yield, confirming the mutualistic character of this interaction. Resequencing of the Si genome using the Oxford Nanopore technique, followed by de novo assembly yielded in 57 contigs and 9441 predicted genes, including putative members of several families involved in sRNA production. Transcriptome analysis at an early stage of the mutualistic interaction identified 2963 differentially expressed genes (DEG) in Si and 317 in Bd line 21-3. The fungal DEGs were largely associated with carbohydrate metabolism, cell wall degradation, and nutrient uptake, while plant DEGs indicated modulation of (a)biotic stress responses and defense pathways. Additionally, 10% of the upregulated fungal DEGs encode candidate protein effectors, including six DELD proteins typical for Sebacinales. Analysis of the global changes in the sRNA profiles of both associated organisms revealed several putative endogenous plant sRNAs expressed during colonization belonging to known micro (mi)RNA families involved in growth and developmental regulation. Among Bd- and Si-generated sRNAs with putative functions in the interacting organism, we identified transcripts for proteins involved in circadian clock and flowering regulation as well as immunity as potential targets of fungal sRNAs, reflecting the beneficial activity of Si. Conclusions We detected beneficial effects of Si colonization on Bd growth and development, and established a novel plant-mutualist interaction model between these organisms. Together, the changes in gene expression and identification of interaction-induced sRNAs in both organisms support sRNA-based regulation of defense responses and plant development in Bd, as well as nutrient acquisition and cell growth in Si. Our data suggests that a Sebacinalean symbiosis involves reciprocal sRNA targeting of genes during the interaction.

scholarly journals Transcriptome profiles of sturgeon lateral line electroreceptor and mechanoreceptor during regeneration

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Jian Wang ◽  
Chengcheng Lu ◽  
Yifan Zhao ◽  
Zhijiao Tang ◽  
Jiakun Song ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Lateral Line ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Sensory Organs ◽  
Specific Expression ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Early Regeneration

Abstract Background The electrosensory ampullary organs (AOs) and mechanosensory neuromasts (NMs) found in sturgeon and some other non-neopterygian fish or amphibians are both originated from lateral line placodes. However, these two sensory organs have characteristic morphological and physiological differences. The molecular mechanisms for the specification of AOs and NMs are not clearly understood. Results We sequenced the transcriptome for neomycin treated sturgeon AOs and NMs in the early regeneration stages, and de novo assembled a sturgeon transcriptome. By comparing the gene expression differences among untreated AOs, NMs and general epithelia (EPs), we located some specific genes for these two sensory organs. In sturgeon lateral line, the voltage-gated calcium channels and voltage-gated potassium channels were predominant calcium and potassium channel subtypes, respectively. And by correlating gene expression with the regeneration process, we predicated several candidate key transcriptional regulation related genes might be involved in AOs and NMs regeneration. Conclusions Genes with specific expression in the two lateral line sensory organs suggests their important roles in mechanoreceptor and electroreceptor formation. The candidate transcriptional regulation related genes may be important for mechano- and electro- receptor specification, in a “dosage-related” manner. These results suggested the molecular basis for specification of these two sensory organs in sturgeon.

scholarly journals Enhancer Deregulation in Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. SCI-38-SCI-38
Author(s):  
Paola Neri
Keyword(s):  
Gene Expression ◽  
Transcriptional Repression ◽  
Gene Expression Regulation ◽  
Therapeutic Targets ◽  
Regulatory Elements ◽  
Dependent Manner ◽  
Cellular Viability ◽  
Direct Role ◽  
Myeloma Cells ◽  
Bet Inhibitors

Abstract The complexity of gene expression regulation is the result of a composite interplay between promoters, enhancers and other cis-acting regulatory elements bound by transcription factors (TFs) that controls the transcriptional activity of genes. Primary tumor cells, in comparison to their healthy counterparts, are known to display altered enhancer repertoires that are associated with tumor-specific transcription. Large groups of transcriptional enhancers cluster together to form super-enhancers (SEs). These elements have been shown to control genes that are important for maintaining cell identity but are also frequently associated with oncogenes as well as translocations that result in aberrant gene expression in cancer. Immunoglobulin (IGH, IGL, IGK) and non-immunoglobulin (PVT1, FAM46C, DUSP22, etc.) enhancers hijacking by variable genes (MYC, MAF, CCND1/2/3, MMSET, IRF4) is a recognized oncogenic driver event in multiple myeloma (MM). However, the identity of the TFs or transcriptional regulatory complexes binding and regulating the activity of these enhancers remains to be fully elucidated and may yield valuable therapeutic targets. In this regard, the bromodomain and extra-terminal (BET) inhibitors have emerged as promising molecules for the treatment of hematologic malignancies. BET family proteins are chromatin adaptors, functionally linked to important pathways for cellular viability and cancer signaling. In particular, BRD4 has a direct role in the transcription regulation of different genes involved in the cell cycle progression and cellular viability. The BET inhibitor JQ1 selectively inhibits BRD4 by competitively binding to the acetyl-lysine recognition pocket of BET bromodomains from chromatin leading to the inhibition of MYC transcription in a dose- and time-dependent manner. Thus, BRD4 has been recently described as a therapeutic target for MM, among other hematologic diseases. Constitutive activation of MYC signaling is detected in more than 60% of patient-derived MM cells and can be involved in the pathogenesis of MM through different mechanisms. One of the most common somatic genomic aberrations in early and late-stage MM is rearrangement or translocation of MYC. Regardless of whether MYC rearrangements occur at early or late stages of MM pathogenesis, MYC rearrangements may provide one of several critical events contributing to increased autonomy and a more aggressive phenotype. Moreover promiscuous rearrangements of the MYC locus are known to hijack enhancers and super-enhancers to dysregulate MYC expression in MM and are involved in its pathogenesis. The development of the immunomodulatory drugs (IMiDs) has contributed significantly to improve the outcomes of MM patients. They possess pleiotropic anti-MM properties and through CRBN binding they induce Ikaros and Aiolos ubiquitylation and proteasomal degradation with an ensuing transcriptional repression of MYC and IRF4, two essential factors for myeloma cells survival. However, is not clear how IKZF1/IKZF3 regulate MYC transcription and how myeloma cells acquire resistance to IMIDs, "beyond CRBN". In addition, acquired resistance to IMIDs and the loss of the transcriptional repression of MYC are nearly universal and occur in spite of sustained IKZF1/3 degradation suggesting that transcriptional rewiring may be sustaining hijacked enhancers activity and transcription of driver oncogenes. In this contest we have recently demonstrated that IMiDs are repressors of IKZF1/3-depedent oncogenic enhancers. Transcriptional plasticity with expression of extra-lineage TFs such as the ETS family member ETV4 sustains oncogenic enhancers in MM overcoming IKAROS and AIOLOS dependency and promoting IMiDs resistance. Therefore defining TFs occupancy and their circuitry at enhancers identifies "non-canonical" (aberrant) myeloma TFs dependency that may be linked to potential therapeutic targets. Disclosures Neri: Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

scholarly journals H3K36 Methylation Reprograms Gene Expression to Drive Early Gametocyte Development in Plasmodium Falciparum

2021 ◽  
Author(s):  
Jessica Connacher ◽  
Gabrielle A Josling ◽  
Lindsey M Orchard ◽  
Janette Reader ◽  
Manuel Llinas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Repression ◽  
Malaria Parasite ◽  
High Throughput Sequencing ◽  
Morphological Changes ◽  
Virulence Gene ◽  
Control Program ◽  
Global Gene Expression ◽  
Stage Ii ◽  
Global Changes

Abstract Background: The Plasmodium sexual gametocyte stages are the only transmissible form of the malaria parasite and are thus responsible for the continued transmission of the disease. Gametocytes undergo extensive functional and morphological changes from commitment to maturity, directed by an equally extensive control program. Several interconnected mechanisms governing sexual commitment have been described. However, the processes that drive the subsequent differentiation and development of the gametocyte remain largely unexplored. Using chromatin immunoprecipitation followed by high-throughput sequencing we describe an association between H3K36 di- and tri-methylation (H3K36me2&3) and the global changes in the transcriptional program driving gametocyte development post-commitment. Results: Here, we show that in stage II gametocytes, H3K36me2&3 are associated with an active repression of genes involved in asexual proliferation and sexual commitment, linking H3K36me2&3 to the transition from early gametocyte differentiation to intermediate development. Specifically, we establish a link between H3K36me2&3 and the repression of genes that are upregulated during commitment once terminal differentiation renders their protein products obsolete in developing gametocytes, thereby securing an appropriate transcriptional environment for intermediate gametocyte development. Lastly, we associate the enhanced potency of JIB-04 in gametocytes with the inhibition of H3K36me2&3 demethylation and a disruption of normal transcriptional programs.Conclusions: Taken together, our results provide the first description of an association between global gene expression reprogramming and histone post-translational modifications during P. falciparum sexual development. In addition to fulfilling the same role in virulence gene regulation as in asexual parasites, the stage II gametocyte-specific abundance of H3K36me2/3 manifests as a largely interdependent enrichment of the two modifications targeted towards genes whose functions become obsolete in post-commitment gametocytes. This contrasts with the broad repression associated with wide-spread H3K36me2 occupancy in asexual parasites, highlighting H3K36me2/3 enrichment as a marker of directed transcriptional repression specific to early gametocytes. The importance of such histone methylation during gametocyte development is underscored by the transcriptional disruption associated with histone demethylase inhibition in P. falciparum gametocytes. By demonstrating the participation of H3K36me2&3 in gametocyte development, we provide a more thorough understanding of the link between epigenetic mechanisms and gene expression in the transmissible stages of the malaria parasite.

Directed De Novo DNA Methylation of a Genomic Locus Leads to Heritable Transcriptional Repression.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 343-343
Author(s):  
Kevin G. Ford ◽  
Paul J. Hurd ◽  
Andrew J. Bannister ◽  
Tony Kouzarides ◽  
Alexander E. Smith
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcriptional Repression ◽  
Cytosine Methylation ◽  
De Novo ◽  
Genomic Locus ◽  
Repressive Chromatin ◽  
First Time ◽  
Dna Cytosine Methylation ◽  
De Novo Methylation

Abstract The ability to impose exogenous targeted epigenetic changes in the genome represents an attractive goal in gene therapy for the heritable repression of target genes, while potentially enabling the generation and subsequent study of the downstream effects of de novo epigenetic events, which are known to occur in disease. Here we demonstrate the ability of zinc-finger peptides to deliver DNA cytosine methylation in vivo to a genomic target promoter, when expressed as fusions with a mutant prokaryotic DNA cytosine methyltransferase enzyme, thus mimicking cellular de novo methylation events. We show for the first time targeted gene silencing in response to directed DNA cytosine methylation via initiation of a repressive chromatin signature at a targeted genomic locus, characterised by elevation of histone H3K9Me2 and reduction of H3K4Me3 levels at that region. This transcriptional repression is maintained in the absence of sustained targeted methyltransferase action, confirming epigenetic maintenance by the cells own machinery. The inherited DNA methylation pattern is restricted to specific target sites, suggesting that the establishment of repressive chromatin structure does not drive further de novo DNA methylation in this system. Therefore, we demonstrate for the first time, targeted DNA methyltransferases as potential tools for the exogenous and heritable control of gene expression at the chromosomal level, while providing the clearest and most direct confirmation to date of the functional and mechanistic consequences of de novo DNA methylation in the cell. This work represents an important step towards the longer term goal of controlling gene expression through the inheritance of a repressive DNA state, as well as providing a valuable tool for studying spatial and temporal issues associated with ‘genuine’ de novo methylation, on transcription and chromatin structure.

Apoptosis and Cell Cycle Regulatory Gene Expression in Adult De Novo Myelodysplastic Syndromes (MDS)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5093-5093
Author(s):  
Christina Economopoulou ◽  
Vassiliki Pappa ◽  
S. Papageorgiou ◽  
F. Kontsioti ◽  
P Economopoulou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Bone Marrow ◽  
Cell Survival ◽  
De Novo ◽  
Granzyme B ◽  
S Phase ◽  
Regulatory Genes ◽  
Fab Classification ◽  
Normal Controls

Abstract Introduction: MDS constitute a heterogeneous group of clonal haematopoietic disorders characterized by ineffective haematopoiesis and an increased risk of transformation to acute myeloid leukaemia. Increased apoptosis has been associated with ineffective progenitor and maturing haematopoietic cell survival and associated cytopenias early in the disease whereas the progression of MDS to AML occurs concomitant with decreased apoptosis and an increased degree of neoplastic cell survival. The aim of the present study was to identify molecular alterations of cell cycle and apoptosis regulatory genes in the bone marrow cells of adult patients with de novo MDS and to correlate these with clinical characteristics. Patients and methods: A total of 60 cases of MDS, 40 males and 20 females, classified according to FAB classification as follows: 17 RA, 5 RARS, 19 RAEB, 9 RAEBT and 10 CMML, were included in our study. Twelve non-Hodgkin’s lymphoma patients without bone marrow involvement were used as normal controls. BM aspirates were obtained at diagnosis from the patients as well as the control group. We used RNAse Protection Assay to detect alterations of expression at the mRNA level of cell cycle regulatory genes, particularly CDK1, CDK2, CDK3, CDK4, p27, p21, PISSLRE, p16, cyclins A, B, C, D1, D2, D3, A1 as well as apoptosis regulatory genes, particularly caspases 1,2,3,5,6,7,8,9, Granzyme B, bclxL, bclxS, bfl1, bik, bak, bax, bcl2, mcl1. Moreover our study included estimation of apoptosis using the Annexin V affinity assay, as well as analysis of cell cycle by determining the percentage of cells in S phase using flow cytometry. Results: The median value of apoptosis for all MDS cases was 2,79% (range 0–34,9). A positive correlation was found between caspases 3, 5, 9, CDKs 1, 2 and 4, as well as p21 expression and the level of apoptosis. The median value of cells in S phase of the cell cycle was 10,6% (range 0,19–27,4). A positive correlation was found between caspase 3 expression levels and S phase. Patients of the IPSS ≥1 score group were associated with higher values of mcl1 gene expression. Cases with bone marrow blasts ≥5% showed higher bclw, mcl1 and bfl1 gene expression values. Regarding FAB classification, CMML correlated with higher cyclin D1 gene expression. bclxL and mcl1 gene median values were found higher in patients with MDS, compared to normal controls. On the contrary CDK3 and p21 gene median values were lower in patients compared to healthy individuals. Multivariate analysis revealed that combined expression of caspases 8, 3, 6, 5, 2, 7 and Granzyme B was lower in MDS patients compared to normals, as well as that combined expression of cyclins B, C, D1 and D2 was higher in patients with abnormal karyotype compatible with a higher proliferation rate and a higher probability of revealing karyotypic abnormalities. Conclusions: Our study demonstrated that the expression of the anti-apoptotic mcl1 was higher in MDS patients with IPSS>1 and the anti-apoptotic genes bclw, mcl1 and bfl1 had higher expression in cases with 35% blasts in the bone marrow. In the myeloproliferative CMML category a significantly higher cyclin D1 expression was found. Taking into consideration the multifactorial pathogenetic features of MDS, we consider the developing understanding of apoptosis and cell cycle function essential, with the view to proceed to molecularly targeted treatment and improved clinical outcome.

scholarly journals Cellular Gene Expression Survey of Vaccinia Virus Infection of Human HeLa Cells

2003 ◽  
Vol 77 (11) ◽  
pp. 6493-6506 ◽  
Author(s):  
Susana Guerra ◽  
Luis A. López-Fernández ◽  
Alberto Pascual-Montano ◽  
Manuel Muñoz ◽  
Keith Harshman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Virus Infection ◽  
Vaccinia Virus ◽  
Family Member ◽  
Hela Cells ◽  
De Novo ◽  
Host Gene ◽  
Global Changes ◽  
Host Gene Expression ◽  
Regulatory Pathways

ABSTRACT Vaccinia virus (VV) is a cytocidal virus that causes major changes in host cell machinery shortly after infecting cells. To define the consequences of virus infection on host gene expression, we used microarrays of approximately 15,000 human cDNAs to examine expression levels of mRNAs isolated at 2, 6, and 16 h postinfection from cultures of infected HeLa cells. The majority of profiling changes during VV infection corresponded to downregulation of genes at 16 h postinfection. Differentially expressed genes were clustered into seven groups to identify common regulatory pathways, with most of them (90%) belonging to clusters 6 and 7, which represent genes whose expression was repressed after infection. Cluster 1, however, contained 37 transcripts (2.81%) showing a robust pattern of induction that was maintained during the course of infection. Genes in cluster 1 included those for Wiskott-Aldrich syndrome protein (WASP) family member WASF1, thymosine, adenosine A2a receptor, glutamate decarboxylase 2, CD-80 antigen, KIAA0888 protein, selenophosphate synthetase, pericentrin, and attractin as well as several expressed sequence tags. We analyzed in more detail the fate of WASP protein in VV-infected cells, because a related family member, N-WASP, is involved in viral motility. WASP protein accumulated in the course of infection; its increase required viral DNA replication and de novo protein synthesis, and it localized in cytoplasmic structures distinct from uninfected cells. This study is the first quantitative analysis of host gene expression following VV infection of cultured human cells, demonstrating global changes in the expression profile, and identifies upregulated genes with potential roles in the virus replication cycle.

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