scholarly journals Contribution of HDAC3 to transcriptional repression by the human papillomavirus 31 E8^E2 protein

2020 ◽  
Vol 101 (7) ◽  
pp. 751-759
Author(s):  
Marcel Dreer ◽  
Saskia Blondzik ◽  
Elke Straub ◽  
Thomas Iftner ◽  
Frank Stubenrauch
Keyword(s):  
Transcription Factors ◽  
Human Papillomavirus ◽  
Histone Deacetylase ◽  
Transcriptional Repression ◽  
Human Papillomaviruses ◽  
Related Protein ◽  
E2 Protein ◽  
Histone Deacetylase 3 ◽  
Cellular Genes ◽  
Cellular Transcription

Human papillomaviruses (HPV) such as HPV16 and HPV31 encode an E8^E2 protein that acts as a repressor of viral replication and transcription. E8^E2′s repression activities are mediated via the interaction with host-cell NCoR (nuclear receptor corepressor)/SMRT (silencing mediator of retinoid and thyroid receptors) corepressor complexes, which consist of NCoR, its homologue SMRT, GPS2 (G-protein pathway suppressor 2), HDAC3 (histone deacetylase 3), TBL1 (transducin b-like protein 1) and its homologue TBLR1 (TBL1-related protein 1). We now provide evidence that transcriptional repression by HPV31 E8^E2 is NCoR/SMRT-dependent but surprisingly always HDAC3-independent when analysing different HPV promoters. This is in contrast to the majority of several cellular transcription factors using NCoR/SMRT complexes whose transcriptional repression activities are both NCoR/SMRT- and HDAC3-dependent. However, NCoR/SMRT-dependent but HDAC3-independent repression has been described for specific cellular genes, suggesting that this may not be specific for HPV promoters but could be a feature of a subset of NCoR/SMRT-HDAC3 regulated genes.

scholarly journals Cellular transcription factors regulate human papillomavirus type 16 gene expression by binding to a subset of the DNA sequences recognized by the viral E2 protein

1999 ◽  
Vol 80 (8) ◽  
pp. 2087-2096 ◽  
Author(s):  
Hannah Lewis ◽  
Kenneth Webster ◽  
Ana-Maria Sanchez-Perez ◽  
Kevin Gaston
Keyword(s):  
Transcription Factors ◽  
Human Papillomavirus ◽  
Dna Sequences ◽  
Hpv 16 ◽  
E2 Protein ◽  
Human Papillomavirus Type 16 ◽  
Binding Factor ◽  
E6 And E7 ◽  
Cellular Transcription ◽  
Site Binding

Human papillomavirus type 16 (HPV-16) is a DNA tumour virus that has been implicated in the development of cervical cancer. The HPV-16 E2 protein binds to four sites that are present upstream of the viral P97 promoter and regulates transcription of the E6 and E7 oncogenes. Here, it is shown that cellular transcription factors bind to two of these E2 sites. One cellular E2 site-binding factor, which is here named CEF-1, binds tightly to E2 site 1. CEF-2, an unrelated cellular E2 site-binding factor, binds tightly to E2 site 3. Transient transfection studies performed in the absence of the E2 protein showed that mutations that blocked the binding of CEF-1 to E2 site 1 or CEF-2 to E2 site 3 significantly reduced P97 promoter activity. Further characterization of CEF-1 indicated that this factor has not previously been identified and that CEF-1 and E2 competed for binding at E2 site 1.

scholarly journals Interaction of the Papillomavirus E8∧E2C Protein with the Cellular CHD6 Protein Contributes to Transcriptional Repression

2010 ◽  
Vol 84 (18) ◽  
pp. 9505-9515 ◽  
Author(s):  
Jasmin Fertey ◽  
Ingo Ammermann ◽  
Michael Winkler ◽  
Reinhard Stöger ◽  
Thomas Iftner ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Transcriptional Repression ◽  
Human Papillomaviruses ◽  
Hpv E6 ◽  
Host Cell Proteins ◽  
E6 And E7 ◽  
Site Competition ◽  
Rna Knockdown ◽  
Cellular Transcription

ABSTRACT Expression of the E6 and E7 oncogenes of high-risk human papillomaviruses (HPV) is controlled by cellular transcription factors and by viral E2 and E8∧E2C proteins, which are both derived from the HPV E2 gene. Both proteins bind to and repress the HPV E6/E7 promoter. Promoter inhibition has been suggested to be due to binding site competition with cellular transcription factors and to interactions of different cellular transcription modulators with the different amino termini of E2 and E8∧E2C. We have now identified the cellular chromodomain helicase DNA binding domain 6 protein (CHD6) as a novel interactor with HPV31 E8∧E2C by using yeast two-hybrid screening. Pull-down and coimmunoprecipitation assays indicate that CHD6 interacts with the HPV31 E8∧E2C protein via the E2C domain. This interaction is conserved, as it occurs also with the E8∧E2C proteins expressed by HPV16 and -18 and with the HPV31 E2 protein. Both RNA knockdown experiments and mutational analyses of the E2C domain suggest that binding of CHD6 to E8∧E2C contributes to the transcriptional repression of the HPV E6/E7 oncogene promoter. We provide evidence that CHD6 is also involved in transcriptional repression but not activation by E2. Taken together our results indicate that the E2C domain not only mediates specific DNA binding but also has an additional role in transcriptional repression by recruitment of the CHD6 protein. This suggests that repression of the E6/E7 promoter by E2 and E8∧E2C involves multiple interactions with host cell proteins through different protein domains.

scholarly journals Targeting of N-CoR and histone deacetylase 3 by the oncoprotein v-ErbA yields a chromatin infrastructure-dependent transcriptional repression pathway

2000 ◽  
Vol 19 (15) ◽  
pp. 4074-4090 ◽  
Author(s):  
Fyodor D. Urnov ◽  
Janet Yee ◽  
Laurent Sachs ◽  
Trevor N. Collingwood ◽  
Anton Bauer ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Transcriptional Repression ◽  
Histone Deacetylase 3

scholarly journals The N-CoR/Histone Deacetylase 3 Complex Is Required for Repression by Thyroid Hormone Receptor

2003 ◽  
Vol 23 (15) ◽  
pp. 5122-5131 ◽  
Author(s):  
Takahiro Ishizuka ◽  
Mitchell A. Lazar
Keyword(s):  
Thyroid Hormone ◽  
Histone Deacetylase ◽  
Hormone Receptor ◽  
Transcriptional Repression ◽  
Thyroid Hormone Receptor ◽  
Histone Deacetylation ◽  
Orphan Receptor ◽  
Small Interfering Rnas ◽  
Histone Deacetylase 3 ◽  
Nonspecific Effects

ABSTRACT Nuclear receptor corepressors (N-CoR) and silencing mediator for retinoid and thyroid receptors (SMRT) have both been implicated in thyroid hormone receptor (TR)-mediated repression. Here we show that endogenous N-CoR, TBL1, and histone deacetylase 3 (HDAC3), but not HDAC1, -2, or -4, are recruited to a stably integrated reporter gene repressed by unliganded TR as well as the orphan receptor RevErb. Unliganded TR also recruits this complex to a transiently transfected reporter, and transcriptional repression is associated with local histone deacetylation that is reversed by the presence of thyroid hormone. Knockdown of N-CoR using small interfering RNAs markedly reduces repression by the TR ligand binding domain in human 293T cells, whereas knockdown of SMRT has little effect. RevErb repression appears to involve both corepressors in this system. Knockdown of HDAC3 markedly reduces repression by both TR and RevErb, while knockdown of HDAC1 or 2 has more modest, partly nonspecific effects. Thus, HDAC3 is critical for repression by multiple nuclear receptors and the N-CoR HDAC3 complex plays a unique and necessary role in TR-mediated gene repression in human 293T cells.

scholarly journals Histone deacetylase 3 is selectively involved in L3MBTL2-mediated transcriptional repression

FEBS Letters ◽  
2010 ◽  
Vol 584 (11) ◽  
pp. 2225-2230 ◽  
Author(s):  
Jung-Yoon Yoo ◽  
Kyung-Chul Choi ◽  
HeeBum Kang ◽  
Young Jun Kim ◽  
Jeongmin Lee ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Transcriptional Repression ◽  
Histone Deacetylase 3

scholarly journals Human Papillomavirus E7 Repression in Cervical Carcinoma Cells Initiates a Transcriptional Cascade Driven by the Retinoblastoma Family, Resulting in Senescence

2006 ◽  
Vol 81 (5) ◽  
pp. 2102-2116 ◽  
Author(s):  
Kimberly Johung ◽  
Edward C. Goodwin ◽  
Daniel DiMaio
Keyword(s):  
Gene Expression ◽  
Human Papillomavirus ◽  
Cervical Carcinoma ◽  
Replicative Senescence ◽  
Human Fibroblasts ◽  
Constitutive Expression ◽  
Carcinoma Cells ◽  
Bovine Papillomavirus ◽  
E2 Protein ◽  
Cellular Genes

ABSTRACT This work demonstrates a central role for the retinoblastoma (Rb) family in driving the transcriptional program of induced and replicative senescence. HeLa cervical carcinoma cells rapidly undergo senescence when the human papillomavirus (HPV) type 18 E7 gene in these cells is repressed by the bovine papillomavirus (BPV) E2 protein. This senescence response requires the endogenous Rb pathway but not the p53 pathway. Microarray analysis 6 days after BPV E2 introduction into HeLa cells identified 224 cellular genes induced by E7 repression and 354 repressed genes. Many repressed genes were involved in cell cycle progression, and numerous induced genes encoded lysosomal proteins. These gene expression changes were blocked by constitutive expression of the wild-type HPV16 E7 or adenovirus E1A gene, but not by E7 or E1A mutants defective for Rb binding. Short hairpin RNAs targeting the Rb family also inhibited these gene expression changes and blocked senescence. Therefore, surprisingly, the transcriptional response to BPV E2 expression was entirely dependent on E7 repression and activation of the Rb family, and the BPV E2 protein did not directly affect the expression of cellular genes. Activation of the Rb family repressed E2F-responsive genes and stimulated transcriptional activators, thereby mobilizing multiple signals, such as repression of B-MYB and DEK, that were independently sufficient to induce senescence. There was extensive overlap between the transcriptional profiles of senescent, late-passage primary human fibroblasts and senescent cervical carcinoma cells, suggesting that this Rb family-mediated transcriptional cascade also plays a central role in replicative senescence.

scholarly journals Characterization of Transcription Factor Binding to Human Papillomavirus Type 16 DNA during Cellular Differentiation

2006 ◽  
Vol 80 (9) ◽  
pp. 4356-4362 ◽  
Author(s):  
Andrew Carson ◽  
Saleem A. Khan
Keyword(s):  
Transcription Factors ◽  
Host Cell ◽  
Human Papillomaviruses ◽  
Host Protein ◽  
Regulatory Sequences ◽  
Regulatory Regions ◽  
Hpv 16 ◽  
Viral Genes ◽  
Cellular Transcription

ABSTRACT Human papillomaviruses (HPVs) require terminal differentiation of the host cell to produce infectious virions. The process of viral maturation involves a variety of changes in the expression/activity of host proteins that lead to high-level replication of the viral genome and expression of the late viral genes. Although the late promoter regions of HPV type 16 (HPV-16) are still not fully characterized, differentiation-dependent regulation of viral genes is thought to involve changes in the binding of host cell transcription factors to the viral promoter and regulatory regions. Currently, very little is known about specific cellular transcription factors involved in this process. We used the Panomics TransSignal protein/DNA array to identify changes in the levels of cellular transcription factors during methylcellulose-induced differentiation of W12 (20863) cells containing HPV-16. We then identified the differentially expressed transcription factors that specifically bind to HPV-16 DNA, including the known promoter and regulatory regions. We have validated the results obtained from the Panomics array by Western blot analysis. Furthermore, by chromatin immunoprecipitation assays, we have shown that many of the transcription factors identified in the above screen bind to the HPV-16 promoter/regulatory sequences in vivo and that the level of this binding is increased during differentiation. This approach identified approximately 30 transcription factors that specifically bind to HPV-16 sequences and may be involved in regulating HPV-16 transcription during differentiation. Although some of these transcription factors have previously been suggested to be involved in HPV-16 transcription, a number of them represent novel viral DNA-host protein interactions.

scholarly journals Ets-2 repressor factor recruits histone deacetylase to silence human cytomegalovirus immediate-early gene expression in non-permissive cells

2005 ◽  
Vol 86 (3) ◽  
pp. 535-544 ◽  
Author(s):  
Edward Wright ◽  
Mark Bain ◽  
Linda Teague ◽  
Jane Murphy ◽  
John Sinclair
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Histone Deacetylase ◽  
Human Cytomegalovirus ◽  
Histone Deacetylation ◽  
Early Gene ◽  
Immediate Early ◽  
Physical Interaction ◽  
Cellular Transcription

Previous work from this laboratory has shown that expression of human cytomegalovirus (HCMV) immediate-early (IE) genes from the major immediate-early promoter (MIEP) is likely to be regulated by chromatin remodelling around the promoter affecting the acetylation state of core histone tails. The HCMV MIEP contains sequences that bind cellular transcription factors responsible for its negative regulation in undifferentiated, non-permissive cells. Ets-2 repressor factor (ERF) is one such factor that binds to such sequences and represses IE gene expression. Although it is not known how cellular transcription factors such as ERF mediate transcriptional repression of the MIEP, it is likely to involve differentiation-specific co-factors. In this study, the mechanism by which ERF represses HCMV IE gene expression was analysed. ERF physically interacts with the histone deacetylase, HDAC1, both in vitro and in vivo and this physical interaction between ERF and HDAC1 mediates repression of the MIEP. This suggests that silencing of viral IE gene expression, associated with histone deacetylation events around the MIEP, is mediated by differentiation-dependent cellular factors such as ERF, which specifically recruit chromatin remodellers to the MIEP in non-permissive cells.

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