Genome-Wide Histone Acetylation Profiling of Herpesvirus saimiri in Human T Cells upon Induction with a Histone Deacetylase Inhibitor

In this study we investigated the effect of histone acetylation on the transcription of adrenergic-induced genes in rat pinealocytes. We found that treatment of pinealocytes with trichostatin A (TSA), a histone deacetylase inhibitor, caused hyperacetylation of histone H3 (H3) Lys14 at nanomolar concentrations. Hyperacetylation of H3 was also observed after treatment with scriptaid, a structurally unrelated histone deacetylase inhibitor. The effects of TSA and scriptaid were inhibitory on the adrenergic induction of arylalkylamine-n-acetyltransferase (aa-nat) mRNA, protein, and enzyme activity, and on melatonin production. TSA at higher concentrations also inhibited the adrenergic induction of mapk phosphatase-1 (mkp-1) and inducible cAMP early repressor mRNAs. In contrast, the effect of TSA on the norepinephrine induction of the c-fos mRNA was stimulatory. Moreover, the effect of TSA on adrenergic-induced gene transcription was dependent on the time of its addition; its effect was only observed during the active phase of transcription. Chromatin immunoprecipitation with antibodies against acetylated Lys14 of H3 showed an increase in DNA recovery of the promoter regions of aa-nat, mkp-1, and c-fos after treatment with TSA. Together, our results demonstrate that histone acetylation differentially influences the transcription of adrenergic-induced genes, an enhancing effect for c-fos but inhibitory for aa-nat, mkp-1, and inducible cAMP early repressor. Moreover, both inhibitory and enhancing effects appear to be mediated through specific modification of promoter-bound histones during gene transcription.

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Histone Deacetylase Inhibitor Modulates NKG2D Receptor Expression and Memory Phenotype of Human Gamma/Delta T Cells Upon Interaction With Tumor Cells

Frontiers in Immunology ◽

10.3389/fimmu.2019.00569 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 7

Author(s):

Jaydeep Bhat ◽

Samuel Dubin ◽

Alexandra Dananberg ◽

Elgar Susanne Quabius ◽

Juergen Fritsch ◽

...

Keyword(s):

T Cells ◽

Tumor Cells ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitor ◽

Receptor Expression ◽

Gamma Delta T Cells ◽

Gamma Delta ◽

Memory Phenotype ◽

Deacetylase Inhibitor ◽

Nkg2d Receptor

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Abstract 643: The histone deacetylase inhibitor Quisinostat augments the anti-tumor reponses of T-cells: Implications in adoptive cell therapy

10.1158/1538-7445.am2014-643 ◽

2014 ◽

Author(s):

David M. Woods ◽

Andressa L. Sodre ◽

Jason B. Brayer ◽

Eduardo M. Sotomayor

Keyword(s):

T Cells ◽

Cell Therapy ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitor ◽

Adoptive Cell Therapy ◽

Deacetylase Inhibitor

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Induction of the NKG2D Ligands Expression by Histone Deacetylase Inhibitor and Its Impact on the Susceptibility of Leukemic Cells to the Cytolytic Activity of NKG2D-Expressing Cells.

Blood ◽

10.1182/blood.v108.11.924.924 ◽

2006 ◽

Vol 108 (11) ◽

pp. 924-924

Author(s):

Naoko Kato ◽

Junji Tanaka ◽

Junichi Sugita ◽

Tomomi Toubai ◽

Yoko Miura ◽

...

Keyword(s):

T Cells ◽

Nk Cells ◽

Histone Deacetylase ◽

Immune Cells ◽

Histone Deacetylase Inhibitor ◽

Cytolytic Activity ◽

Leukemic Cells ◽

Expression Levels ◽

Nkg2d Ligands ◽

Deacetylase Inhibitor

Abstract Innate immune cells such as natural killer (NK) cells play a crucial rule in antitumor immune responses. NK cells have functionally opposite receptors for activating and inhibiting signals to exert cytotoxicity. NKG2D is a C-type lectin-like activating receptor and is expressed in various immune cells, including NK cells, NKT cells, CD8+α/β+T cells, and γ/δ+T cells. NKG2D recognizes its ligands, MHC class I-related chain A and B (MICA, MICB). NKG2D ligands are not present on normal cells but are induced by various stresses such as viral infection. Moreover NKG2D ligands are expressed in many malignant cells including hematological malignancies. It has been suggested that involvement of NKG2D in NK or CD8+Tcell-mediated cytotoxicity correlates with the expression levels of ligands on target cells. Therefore induction of NKG2D ligands may lead to enhance the sensitivity to NKG2D-mediated cytotoxicity. In this study, we could enhance expression levels of MICA and MICB by treatment with the histone deacetylase inhibitor trichostatin A (TsA) in lymphoid leukemic cell line BALL1 and some primary patients’ lymphoid leukemic cells. Treatment of BALL1 and patients’ leukemic cells with TsA for 12 hr increased MICA and MICB mRNA expression at least by more than 2 fold by Real-time PCR. Treatment of BALL1 with TsA for 12 hr increased MICA and MICB protein expression on the cell surface by more than 2 fold by flow cytometry analysis. These results suggested that expression of MICA and MICB is partly regulated by histone acetylation. Chromatin immunoprecipitation assay revealed that treatment with TsA resulted in increased acetylation of histone H3 and decreased association with the counteracting enzymes of histone acetyltransferases HDAC1 at the MICA and MICB promoter in BALL1 cell and patients’ leukemic cells. To examine the impact of the cytolytic activity of NKG2D-expressing cells on leukemic cells in which expression of NKG2D ligands was induced by TsA treatment, we performed standard 4 hr 51Cr release assays using BALL1 cells and patients’ leukemic cells. Up-regulation of NKG2D ligands by TsA treatment led to enhance the susceptibility of BALL1 and patients’ leukemic cells by 2 or 3 times to the cytolytic activity of NKG2D-expressing cells. Blocking experiment using specific antibodies for MICA and MICB inhibited the NKG2D-expressing cell-mediated cytolytic activity against BALL1 cells. Our results suggest that regulation of NKG2D ligands expression by treatment with chromatin-remodeling drugs may be an effective strategy to enhance the susceptibility of leukemic cells to the cytolytic activity of NKG2D-expressing cells for immunotherapy.

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