scholarly journals Human MI-ER1 Alpha and Beta Function as Transcriptional Repressors by Recruitment of Histone Deacetylase 1 to Their Conserved ELM2 Domain

2003 ◽  
Vol 23 (1) ◽  
pp. 250-258 ◽  
Author(s):  
Zhihu Ding ◽  
Laura L. Gillespie ◽  
Gary D. Paterno
Keyword(s):  
Histone Deacetylase ◽  
Trichostatin A ◽  
Beta Function ◽  
Amino Acid Level ◽  
Early Gene ◽  
Regulation Of Transcription ◽  
Embryonic Cells ◽  
Histone Deacetylase 1 ◽  
Human Orthologue ◽  
Breast Carcinoma Cell Lines

ABSTRACT mi-er1 (previously called er1) was first isolated from Xenopus laevis embryonic cells as a novel fibroblast growth factor-regulated immediate-early gene. Xmi-er1 was shown to encode a nuclear protein with an N-terminal acidic transcription activation domain. The human orthologue of mi-er1 (hmi-er1) displays 91% similarity to the Xenopus sequence at the amino acid level and was shown to be upregulated in breast carcinoma cell lines and tumors. Alternative splicing at the 3′ end of hmi-er1 produces two major isoforms, hMI-ER1α and hMI-ER1β, which contain distinct C-terminal domains. In this study, we investigated the role of hMI-ER1α and hMI-ER1β in the regulation of transcription. Using fusion proteins of hMI-ER1α or hMI-ER1β tethered to the GAL4 DNA binding domain, we show that both isoforms, when recruited to the G5tkCAT minimal promoter, function to repress transcription. We demonstrate that this repressor activity is due to interaction and recruitment of a trichostatin A-sensitive histone deacetylase 1 (HDAC1). Furthermore, deletion analysis revealed that recruitment of HDAC1 to hMI-ER1α and hMI-ER1β occurs through their common ELM2 domain. The ELM2 domain was first described in the Caenorhabditis elegans Egl-27 protein and is present in a number of SANT domain-containing transcription factors. This is the first report of a function for the ELM2 domain, highlighting its role in the regulation of transcription.

Abstract 141: Histone Deacetylase 1 Regulates Nitric Oxide Production and Nitric Oxide Synthase-3 Acetylation in Endothelial Cells

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Kelly A Hyndman ◽  
Dao H Ho ◽  
Jennifer S Pollock
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Histone Deacetylase ◽  
Life Stress ◽  
Trichostatin A ◽  
Early Life Stress ◽  
No Production ◽  
Histone Deacetylase 1 ◽  
Nitrite Production

Previous reports showed that NOS3 is regulated by acetylation through transcriptional mechanisms via histone acetylation or through direct lysine acetylation. Histone deacetylase (HDAC) enzymes and histone acetyltransferases (HATs) modulate acetylation processes. Recent work by our lab, demonstrated increased expression of aortic HDAC1 and HDAC6 while HATs were unchanged in a mouse model of early life stress with endothelial dysfunction. These data suggest a negative correlation between endothelial dysfunction and HDAC expression. The purpose of this study was to test the hypothesis that HDAC1 and 6 regulate endothelial NO production and/or NOS3 acetylation. Initial immunoprecipitation studies with anti-acetyl lysine and anti-NOS3 antibodies demonstrated that NOS3 is basally acetylated in primary bovine aortic endothelial cells (BAECs). Treatment with the HDAC inhibitor, trichostatin A (500 nM) for 1 hr, significantly increased NOS3 acetylation. BAECs were transfected with HDAC1, HDAC6, vector expression plasmids, or untransfected, with nitrite production determined by HPLC and NOS3 acetylation and expression probed by immunoprecipitation and Western blotting. Untransfected and vector transfected control BAECs had similar NO production (357 ± 10 and 344 ± 30 pmol/mg pr/h, respectively, N=6) as well as NOS3 acetylation (7.8 ± 1.6 and 6.8 ±0.3 AU, N=3). HDAC6 transfected BAECs had similar NO production to the control BAECs (272 ± 93 pmol/mg pr/h, N=3) with an increase in NOS3 acetylation (17.4 ± 1.7 AU, N=3). In contrast, HDAC1 overexpression significantly decreased NO production (89 ± 50 pmol/mg pr/h, P< 0.05, N=3) and reduced NOS3 acetylation (3.8 ± 0.5 A.U, N=3), P <0.05). Control transfections, HDAC6, and HDAC1 transfected BAECS all had similar NOS3 expression (10.14 ± 1.8; 9.8 ±1.6; 8.9 ± 1.5; 10.6 ± 1.0 AU, respectively, N=3). Thus, we conclude that HDAC1 regulates NO production via direct lysine deacetylation of NOS3.

scholarly journals Histone Deacetylase 1 Can Repress Transcription by Binding to Sp1

1999 ◽  
Vol 19 (8) ◽  
pp. 5504-5511 ◽  
Author(s):  
Angelika Doetzlhofer ◽  
Hans Rotheneder ◽  
Gerda Lagger ◽  
Manfred Koranda ◽  
Vladislav Kurtev ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Histone Deacetylase ◽  
Transcriptional Repression ◽  
Trichostatin A ◽  
Dependent Manner ◽  
Histone Deacetylase 1 ◽  
3T3 Fibroblasts ◽  
C Terminus ◽  
Histone Deacetylase Inhibitor Trichostatin ◽  
Carboxy Terminal

ABSTRACT The members of the Sp1 transcription factor family can act as both negative and positive regulators of gene expression. Here we show that Sp1 can be a target for histone deacetylase 1 (HDAC1)-mediated transcriptional repression. The histone deacetylase inhibitor trichostatin A activates the chromosomally integrated murine thymidine kinase promoter in an Sp1-dependent manner. Coimmunoprecipitation experiments with Swiss 3T3 fibroblasts and 293 cells demonstrate that Sp1 and HDAC1 can be part of the same complex. The interaction between Sp1 and HDAC1 is direct and requires the carboxy-terminal domain of Sp1. Previously we have shown that the C terminus of Sp1 is necessary for the interaction with the transcription factor E2F1 (J. Karlseder, H. Rotheneder, and E. Wintersberger, Mol. Cell. Biol. 16:1659–1667, 1996). Coexpression of E2F1 interferes with HDAC1 binding to Sp1 and abolishes Sp1-mediated transcriptional repression. Our results indicate that one component of Sp1-dependent gene regulation involves competition between the transcriptional repressor HDAC1 and the transactivating factor E2F1.

scholarly journals Histone Deacetylase 1 Inactivation by an Adenovirus Early Gene Product

2002 ◽  
Vol 12 (7) ◽  
pp. 594-598 ◽  
Author(s):  
Susanna Chiocca ◽  
Vladislav Kurtev ◽  
Riccardo Colombo ◽  
Roberto Boggio ◽  
M. Teresa Sciurpi ◽  
...  
Keyword(s):  
Gene Product ◽  
Histone Deacetylase ◽  
Early Gene ◽  
Histone Deacetylase 1

scholarly journals Respiratory Syncytial Virus-Inducible BCL-3 Expression Antagonizes the STAT/IRF and NF-κB Signaling Pathways by Inducing Histone Deacetylase 1 Recruitment to the Interleukin-8 Promoter

2005 ◽  
Vol 79 (24) ◽  
pp. 15302-15313 ◽  
Author(s):  
Mohammad Jamaluddin ◽  
Sanjeev Choudhary ◽  
Shaofei Wang ◽  
Antonella Casola ◽  
Ruksana Huda ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Signaling Pathways ◽  
Histone Deacetylase ◽  
Trichostatin A ◽  
A549 Cells ◽  
B Cell Lymphoma ◽  
Interleukin 8 ◽  
Nuclear Targeting ◽  
Histone Deacetylase 1 ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is a paramyxovirus that produces airway inflammation, in part by inducing interleukin-8 (IL-8) expression, a CXC-type chemokine, via the NF-κB/RelA and STAT/IRF signaling pathways. In RSV-infected A549 cells, IL-8 transcription attenuates after 24 h in spite of ongoing viral replication and persistence of nuclear RelA, suggesting a mechanism for transcriptional attenuation. RSV infection induces B-cell lymphoma protein -3 (Bcl-3) expression 6 to 12 h after viral infection, at times when IL-8 transcription is inhibited. By contrast, 293 cells, deficient in inducible Bcl-3 expression, show no attenuation of IL-8 transcription. We therefore examined Bcl-3's role in terminating virus-inducible IL-8 transcription. Transient expression of Bcl-3 potently inhibited virus-inducible IL-8 transcription by disrupting both the NF-κB and STAT/IRF pathways. Although previously Bcl-3 was thought to capture 50-kDa NF-κB1 isoforms in the cytoplasm, immunoprecipitation (IP) and electrophoretic mobility shift assays indicate that nuclear Bcl-3 associates with NF-κB1 without affecting DNA binding. Additionally, Bcl-3 potently inhibited the STAT/IRF pathway. Nondenaturing co-IP assays indicate that nuclear Bcl-3 associates with STAT-1 and histone deacetylase 1 (HDAC-1), increasing HDAC-1 recruitment to the IL-8 promoter. Treatment with the HDAC inhibitor trichostatin A blocks attenuation of IL-8 transcription. A nuclear targeting-deficient Bcl-3 is unable to enhance HDAC-1-mediated chemokine repression. Finally, small inhibitory RNA-mediated Bcl-3 “knockdown” resulted in enhanced RSV-induced chemokine expression in A549 cells. These data indicate that Bcl-3 is a virus-inducible inhibitor of chemokine transcription by interfering with the NF-κB and STAT/IRF signaling pathways by complexing with them and recruiting HDAC-1 to attenuate target promoter activity.

scholarly journals Corepressor MMTR/DMAP1 Is Involved in both Histone Deacetylase 1- and TFIIH-Mediated Transcriptional Repression

2007 ◽  
Vol 27 (10) ◽  
pp. 3578-3588 ◽  
Author(s):  
Bong Gu Kang ◽  
June Ho Shin ◽  
Jae Kyu Yi ◽  
Ho Chul Kang ◽  
Jong Joo Lee ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Transcriptional Repression ◽  
Trichostatin A ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Dominant Negative ◽  
Luciferase Reporter ◽  
Histone Deacetylase 1 ◽  
Wide Range

ABSTRACT A transcription corepressor, MAT1-mediated transcriptional repressor (MMTR), was found in mouse embryonic stem cell lines. MMTR orthologs (DMAP1) are found in a wide variety of life forms from yeasts to humans. MMTR down-regulation in differentiating mouse embryonic stem cells in vitro resulted in activation of many unrelated genes, suggesting its role as a general transcriptional repressor. In luciferase reporter assays, the transcriptional repression activity resided at amino acids 221 to 468. Histone deacetylase 1 (HDAC1) interacts with MMTR both in vitro and in vivo and also interacts with MMTR in the nucleus. Interestingly, MMTR activity was only partially rescued by competition with dominant-negative HDAC1(H141A) or by treatment with an HDAC inhibitor, trichostatin A (TSA). To identify the protein responsible for HDAC1-independent MMTR activity, we performed a yeast two-hybrid screen with the full-length MMTR coding sequence as bait and found MAT1. MAT1 is an assembly/targeting factor for cyclin-dependent kinase-activating kinase which constitutes a subcomplex of TFIIH. The coiled-coil domain in the middle of MAT1 was confirmed to interact with the C-terminal half of MMTR, and the MMTR-mediated transcriptional repression activity was completely restored by MAT1 in the presence of TSA. Moreover, intact MMTR was required to inhibit phosphorylation of the C-terminal domain in the RNA polymerase II largest subunit by TFIIH kinase in vitro. Taken together, these data strongly suggest that MMTR is part of the basic cellular machinery for a wide range of transcriptional regulation via interaction with TFIIH and HDAC.

scholarly journals Autoregulation of Mouse Histone Deacetylase 1 Expression

2003 ◽  
Vol 23 (19) ◽  
pp. 6993-7004 ◽  
Author(s):  
Bernd Schuettengruber ◽  
Elisabeth Simboeck ◽  
Harald Khier ◽  
Christian Seiser
Keyword(s):  
Histone Deacetylase ◽  
Binding Sites ◽  
Mammalian Cells ◽  
Promoter Activity ◽  
Cell Cycle Progression ◽  
Trichostatin A ◽  
Consensus Sequence ◽  
Histone Deacetylase 1 ◽  
Deacetylase Inhibitor ◽  
Ccaat Box

ABSTRACT Histone deacetylase 1 (HDAC1) is a major regulator of chromatin structure and gene expression. Tight control of HDAC1 expression is essential for development and normal cell cycle progression. In this report, we analyzed the regulation of the mouse HDAC1 gene by deacetylases and acetyltransferases. The murine HDAC1 promoter lacks a TATA box consensus sequence but contains several putative SP1 binding sites and a CCAAT box, which is recognized by the transcription factor NF-Y. HDAC1 promoter-reporter studies revealed that the distal SP1 site and the CCAAT box are crucial for HDAC1 promoter activity and act synergistically to constitute HDAC1 promoter activity. Furthermore, these sites are essential for activation of the HDAC1 promoter by the deacetylase inhibitor trichostatin A (TSA). Chromatin immunoprecipitation assays showed that HDAC1 is recruited to the promoter by SP1 and NF-Y, thereby regulating its own expression. Coexpression of acetyltransferases elevates HDAC1 promoter activity when the SP1 site and the CCAAT box are intact. Increased histone acetylation at the HDAC1 promoter region in response to TSA treatment is dependent on binding sites for SP1 and NF-Y. Taken together, our results demonstrate for the first time the autoregulation of a histone-modifying enzyme in mammalian cells.

Msx3 protein recruits histone deacetylase to down-regulate the Msx1 promoter

2000 ◽  
Vol 353 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Ritcha MEHRA-CHAUDHARY ◽  
Hideo MATSUI ◽  
Rajendra RAGHOW
Keyword(s):  
Histone Deacetylase ◽  
Binding Protein ◽  
Trichostatin A ◽  
Camp Response Element Binding ◽  
C2c12 Cells ◽  
Dependent Manner ◽  
Camp Response Element ◽  
Histone Deacetylase 1 ◽  
Element Binding Protein ◽  
Dual Mechanism

Msx1 promoter is known to be repressed by Msx1 protein [Shetty, Takahashi, Matsui, Iyengar and Raghow (1999) Biochem. J. 339, 751–758]. We show that in the transiently transfected C2C12 myoblasts, co-expression of Msx3 also causes potent repression of Msx1 promoter that can be relieved by exogenous expression of cAMP-response-element-binding protein-binding protein (CBP) and p300 in a dose-dependent manner. Co-immunoprecipitation and Western blot analyses revealed that Msx3 interacts with CBP and p300 and this interaction significantly decreases the histone acetyltransferase (HAT) activity of both proteins. We also discovered that Msx3-mediated repression of Msx1 promoter is synergized by the exogenous co-expression of histone deacetylase 1 (HDAC1). Furthermore, the repression of Msx1 promoter by Msx3 could be relieved by treating transfected cells with trichostatin A, an inhibitor of HDAC(s). Finally, we show that Msx3 and HDAC1 can be co-immunoprecipitated in a complex that does not contain CBP and that Msx3 and HDAC1 proteins are co-localized in the nucleus. Taken together, our results strongly suggest that two distinct multiprotein complexes are present within the nuclei of C2C12 cells: one containing Msx3 and HDAC(s) and another containing Msx3 and CBP and/or p300. On the basis of these results, we propose a dual mechanism of repression by Msx3 protein that involves the squelching of the HAT activity of co-activators, CBP and p300, and recruitment of HDAC(s).

scholarly journals Snail Mediates E-Cadherin Repression by the Recruitment of the Sin3A/Histone Deacetylase 1 (HDAC1)/HDAC2 Complex

2004 ◽  
Vol 24 (1) ◽  
pp. 306-319 ◽  
Author(s):  
Hector Peinado ◽  
Esteban Ballestar ◽  
Manel Esteller ◽  
Amparo Cano
Keyword(s):  
Transcription Factor ◽  
Causal Relationship ◽  
Histone Deacetylase ◽  
Trichostatin A ◽  
Hdac Activity ◽  
Histone Deacetylase 1 ◽  
Acetylation Status ◽  
Direct Causal Relationship ◽  
E Cadherin

ABSTRACT The transcription factor Snail has been described as a direct repressor of E-cadherin expression during development and carcinogenesis; however, the specific mechanisms involved in this process remain largely unknown. Here we show that mammalian Snail requires histone deacetylase (HDAC) activity to repress E-cadherin promoter and that treatment with trichostatin A (TSA) is sufficient to block the repressor effect of Snail. Moreover, overexpression of Snail is correlated with deacetylation of histones H3 and H4 at the E-cadherin promoter, and TSA treatment in Snail-expressing cells reverses the acetylation status of histones. Additionally, we demonstrate that Snail interacts in vivo with the E-cadherin promoter and recruits HDAC activity. Most importantly, we demonstrate an interaction between Snail, histone deacetylase 1 (HDAC1) and HDAC2, and the corepressor mSin3A. This interaction is dependent on the SNAG domain of Snail, indicating that the Snail transcription factor mediates the repression by recruitment of chromatin-modifying activities, forming a multimolecular complex to repress E-cadherin expression. Our results establish a direct causal relationship between Snail-dependent repression of E-cadherin and the modification of chromatin at its promoter.

scholarly journals Counterregulation of Chromatin Deacetylation and Histone Deacetylase Occupancy at the Integrated Promoter of Human Immunodeficiency Virus Type 1 (HIV-1) by the HIV-1 Repressor YY1 and HIV-1 Activator Tat

2002 ◽  
Vol 22 (9) ◽  
pp. 2965-2973 ◽  
Author(s):  
Guocheng He ◽  
David M. Margolis
Keyword(s):  
Human Immunodeficiency Virus ◽  
Histone Deacetylase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Trichostatin A ◽  
Dominant Negative Mutant ◽  
Histone Deacetylase 1 ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Repression of human immunodeficiency virus type 1 (HIV-1) transcription may contribute to the establishment or maintenance of proviral quiescence in infected CD4+ cells. The host factors YY1 and LSF cooperatively recruit histone deacetylase 1 (HDAC1) to the HIV-1 long terminal repeat (LTR) and inhibit transcription. We demonstrate here regulation of occupancy of HDAC1 at a positioned nucleosome (nuc 1) near the transcription start site of integrated LTR. We find that expression of YY1 increases occupancy by HDAC1, decreases acetylation at nuc 1, and downregulates LTR expression. HDAC1 recruitment and histone hypoacetylation were also seen when Tat activation was inhibited by the overexpression of YY1. A YY1 mutant without an HDAC1 interaction domain and incompetent to inhibit LTR activation fails to recruit HDAC1 to LTR or decrease nuc 1 acetylation. Further, expression of a dominant-negative mutant of LSF (dnLSF), which inhibits LSF occupancy and LTR repression, results in acetylation and decreased HDAC1 occupancy at nuc 1. Conversely, exposure of cells to the histone deacetylase inhibitor trichostatin A or activation of LTR expression by HIV-1 Tat results in the displacement of HDAC1 from nuc 1, in association with increased acetylation of histone H4. Recruitment of HDAC1 to the LTR nuc 1 can counteract Tat activation and repress LTR expression. Significantly, when repression is overcome, LTR activation is associated with decreased HDAC1 occupancy. Since the persistence of integrated HIV-1 genomes despite potent suppression of viral replication is a major obstacle for current antiretroviral therapy, strategies to selectively disrupt the quiescence of chromosomal provirus may play a role in the future treatment of AIDS.

scholarly journals Activation of the Mouse Histone Deacetylase 1 Gene by Cooperative Histone Phosphorylation and Acetylation

2002 ◽  
Vol 22 (22) ◽  
pp. 7820-7830 ◽  
Author(s):  
Christoph Hauser ◽  
Bernd Schuettengruber ◽  
Stefan Bartl ◽  
Gerda Lagger ◽  
Christian Seiser
Keyword(s):  
Growth Factors ◽  
Histone Deacetylase ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Trichostatin A ◽  
Histone H3 ◽  
Mitogen Activated Protein Kinase ◽  
Activity Levels ◽  
Mrna Levels ◽  
Histone Deacetylase 1

ABSTRACT Histone deacetylase 1 (HDAC1) is a major regulator of chromatin structure and gene expression. Tight control of HDAC1 expression is essential for normal cell cycle progression of mammalian cells. HDAC1 mRNA levels are regulated by growth factors and by changes in intracellular deacetylase activity levels. Stimulation of the mitogen-activated protein kinase cascade by anisomycin or growth factors, together with inhibition of deacetylases by trichostatin A (TSA), leads to stable histone H3 phosphoacetylation and strongly induced HDAC1 expression. In contrast, activation of the nucleosomal response by anisomycin alone results only in transient phosphoacetylation of histone H3 without affecting HDAC1 mRNA levels. The transcriptional induction of the HDAC1 gene by anisomycin and TSA is efficiently blocked by H89, an inhibitor of the nucleosomal response. Detailed studies of the kinetics of histone acetylation and phosphorylation show that the two modifications are synergistic and essential for induced HDAC1 transcription. Activation of the HDAC1 gene by anisomycin together with TSA or by growth factors is accompanied by phosphoacetylation of HDAC1 promoter-associated histone H3. Our results present evidence for a precise regulatory mechanism which allows induction of the HDAC1 gene in response to proliferation signals and modulation of HDAC1 expression dependent on intracellular deacetylase levels.

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