scholarly journals Histone Deacetylase 1 Reduces Lipogenesis by Suppressing SREBP1 Transcription in Human Sebocyte Cell Line SZ95

2021 ◽  
Vol 22 (9) ◽  
pp. 4477
Author(s):  
Hye Sun Shin ◽  
Yuri Lee ◽  
Mi Hee Shin ◽  
Soo Ick Cho ◽  
Christos C. Zouboulis ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Cell Line ◽  
Histone Deacetylase ◽  
Fatty Acid Synthase ◽  
Skin Diseases ◽  
Trichostatin A ◽  
Critical Role ◽  
Histone Deacetylase 1 ◽  
Lipogenic Genes ◽  
Sebum Production

Proper regulation of sebum production is important for maintaining skin homeostasis in humans. However, little is known about the role of epigenetic regulation in sebocyte lipogenesis. We investigated histone acetylation changes and their role in key lipogenic gene regulation during sebocyte lipogenesis using the human sebaceous gland cell line SZ95. Sebocyte lipogenesis is associated with a significant increase in histone acetylation. Treatment with anacardic acid (AA), a p300 histone acetyltransferase inhibitor, significantly decreased the lipid droplet number and the expression of key lipogenic genes, including sterol regulatory-binding protein 1 (SREBP1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). In contrast, treatment with trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, increased the expression of these genes. Global HDAC enzyme activity was decreased, and HDAC1 and HDAC2 expression was downregulated during sebaceous lipogenesis. Interestingly, HDAC1 knockdown increased lipogenesis through SREBP1 induction, whereas HDAC1 overexpression decreased lipogenesis and significantly suppressed SREBP1 promoter activity. HDAC1 and SREBP1 levels were inversely correlated in human skin sebaceous glands as demonstrated in immunofluorescence images. In conclusion, HDAC1 plays a critical role in reducing SREBP1 transcription, leading to decreased sebaceous lipogenesis. Therefore, HDAC1 activation could be an effective therapeutic strategy for skin diseases related to excessive sebum production.

scholarly journals BRG-1 Is Recruited to Estrogen-Responsive Promoters and Cooperates with Factors Involved in Histone Acetylation

2000 ◽  
Vol 20 (20) ◽  
pp. 7541-7549 ◽  
Author(s):  
James DiRenzo ◽  
Yongfeng Shang ◽  
Michael Phelan ◽  
Säid Sif ◽  
Molly Myers ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Nuclear Receptors ◽  
Transcriptional Activation ◽  
Trichostatin A ◽  
Critical Role ◽  
Histone Deacetylation ◽  
Estrogen Signaling ◽  
Creb Binding Protein ◽  
Histone Deacetylase 1 ◽  
Acetylation State

ABSTRACT Several factors that mediate activation by nuclear receptors also modify the chemical and structural composition of chromatin. Prominent in this diverse group is the steroid receptor coactivator 1 (SRC-1) family, which interact with agonist-bound nuclear receptors, thereby coupling them to multifunctional transcriptional coregulators such as CREB-binding protein (CBP), p300, and PCAF, all of which have potent histone acetyltransferase activity. Additionally factors including the Brahma-related gene 1 (BRG-1) that are involved in the structural remodeling of chromatin also mediate hormone-dependent transcriptional activation by nuclear receptors. Here, we provide evidence that these two distinct mechanisms of coactivation may operate in a collaborative manner. We demonstrate that transcriptional activation by the estrogen receptor (ER) requires functional BRG-1 and that the coactivation of estrogen signaling by either SRC-1 or CBP is BRG-1 dependent. We find that in response to estrogen, ER recruits BRG-1, thereby targeting BRG-1 to the promoters of estrogen-responsive genes in a manner that occurs simultaneous to histone acetylation. Finally, we demonstrate that BRG-1-mediated coactivation of ER signaling is regulated by the state of histone acetylation within a cell. Inhibition of histone deacetylation by trichostatin A dramatically increases BRG-1-mediated coactivation of ER signaling, and this increase is reversed by overexpression of histone deacetylase 1. These studies support a critical role for BRG-1 in ER action in which estrogen stimulates an ER–BRG-1 association coupling BRG-1 to regions of chromatin at the sites of estrogen-responsive promoters and promotes the activity of other recruited factors that alter the acetylation state of chromatin.

scholarly journals Effects of histone deacetylase inhibitors on estradiol-induced proliferation and hyperplasia formation in the mouse uterus

2005 ◽  
Vol 185 (3) ◽  
pp. 539-549 ◽  
Author(s):  
Andrei G Gunin ◽  
Irina N Kapitova ◽  
Nina V Suslonova
Keyword(s):  
Estrogen Receptor ◽  
Histone Acetylation ◽  
Histone Deacetylase ◽  
Sodium Butyrate ◽  
Histone Deacetylase Inhibitors ◽  
Trichostatin A ◽  
Progesterone Receptors ◽  
Estrogen Receptor Α ◽  
Mouse Uterus ◽  
Myometrial Cells

It is suggested that estrogen hormones recruit mechanisms controlling histone acetylation to bring about their effects in the uterus. However, it is not known how the level of histone acetylation affects estrogen-dependent processes in the uterus, especially proliferation and morphogenetic changes. Therefore, this study examined the effects of histone deacetylase blockers, trichostatin A and sodium butyrate, on proliferative and morphogenetic reactions in the uterus under long-term estrogen treatment. Ovari-ectomized mice were treated with estradiol dipropionate (4 μg per 100 g; s.c., once a week) or vehicle and trichostatin A (0.008 mg per 100 g; s.c., once a day) or sodium butyrate (1% in drinking water), or with no additional treatments for a month. In animals treated with estradiol and trichostatin A or sodium butyrate, uterine mass was increased, and abnormal uterine glands and atypical endometrial hyperplasia were found more often. Both histone deacetylase inhibitors produced an increase in the numbers of mitotic and bromodeoxyuridine-labelled cells in luminal and glandular epithelia, in stromal and myometrial cells. Levels of estrogen receptor-α and progesterone receptors in uterine epithelia, stromal and myometrial cells were decreased in mice treated with estradiol and trichostatin A or sodium butyrate. Expression of β-catenin in luminal and glandular epithelia was attenuated in mice treated with estradiol with trichostatin A or sodium butyrate. Both histone deacetylase inhibitors have similar unilateral effects; however the action of trichostatin A was more expressed than that of sodium butyrate. Thus, histone deacetylase inhibitors exert proliferative and morphogenetic effects of estradiol. The effects of trichostatin A and sodium butyrate are associated with changes in expression of estrogen receptor-α, progesterone receptors and β-catenin in the uterus.

scholarly journals Acetylation of Histone H3 and Adrenergic-Regulated Gene Transcription in Rat Pinealocytes

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 4592-4600 ◽  
Author(s):  
A. K. Ho ◽  
D. M. Price ◽  
W. G. Dukewich ◽  
N. Steinberg ◽  
T. G. Arnason ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Histone Deacetylase ◽  
Gene Transcription ◽  
Histone Deacetylase Inhibitor ◽  
Trichostatin A ◽  
Histone H3 ◽  
Dna Recovery ◽  
Inducible Camp Early Repressor ◽  
Deacetylase Inhibitor ◽  
Induced Genes

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.

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 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.

scholarly journals Histone deacetylase inhibitors upregulate Rap1GAP and inhibit Rap activity in thyroid tumor cells

2011 ◽  
Vol 18 (3) ◽  
pp. 301-310 ◽  
Author(s):  
Xiaoyun Dong ◽  
Christopher Korch ◽  
Judy L Meinkoth
Keyword(s):  
Thyroid Carcinoma ◽  
Cell Line ◽  
Tumor Cells ◽  
Histone Deacetylase ◽  
Cell Lines ◽  
Trichostatin A ◽  
Hdac Inhibitors ◽  
Thyroid Tumor ◽  
Human Thyroid ◽  
Demethylating Agent

Increases in Rap activity have been associated with tumor progression. Although activating mutations in Rap have not been described, downregulation of Rap1GAP is frequent in human tumors including thyroid carcinomas. In this study, we explored whether endogenous Rap1GAP expression could be restored to thyroid tumor cells. The effects of deacetylase inhibitors and a demethylating agent, individually and in combination, were examined in four differentiated and six anaplastic thyroid carcinoma (ATC) cell lines. Treatment with the structurally distinct histone deacetylase (HDAC) inhibitors, sodium butyrate and trichostatin A, increased Rap1GAP expression in all the differentiated thyroid carcinoma cell lines and in four of the six ATC cell lines. The demethylating agent, 5-aza-deoxycytidine, restored Rap1GAP expression in one anaplastic cell line and enhanced the effects of HDAC inhibitors in a second anaplastic cell line. Western blotting indicated that Rap2 was highly expressed in human thyroid cancer cells. Importantly, treatment with HDAC inhibitors impaired Rap2 activity in both differentiated and anaplastic tumor cell lines. The mechanism through which Rap activity is repressed appears to entail effects on the expression of multiple Rap regulators, including RapGEFs and RapGAPs. These results suggest that HDAC inhibitors may provide a tractable approach to impair Rap activity in human tumor cells.

scholarly journals Dynamic Analysis of Proviral Induction and De Novo Methylation: Implications for a Histone Deacetylase-Independent, Methylation Density-Dependent Mechanism of Transcriptional Repression

2000 ◽  
Vol 20 (3) ◽  
pp. 842-850 ◽  
Author(s):  
Matthew C. Lorincz ◽  
Dirk Schübeler ◽  
Scott C. Goeke ◽  
Mark Walters ◽  
Mark Groudine ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone Acetylation ◽  
Histone Deacetylase ◽  
Transcriptional Repression ◽  
Mammalian Cells ◽  
Fluorescent Protein ◽  
De Novo ◽  
Trichostatin A ◽  
Histone Deacetylation ◽  
Over Time

ABSTRACT Methylation of cytosines in the CpG dinucleotide is generally associated with transcriptional repression in mammalian cells, and recent findings implicate histone deacetylation in methylation-mediated repression. Analyses of histone acetylation in in vitro-methylated transfected plasmids support this model; however, little is known about the relationships among de novo DNA methylation, transcriptional repression, and histone acetylation state. To examine these relationships in vivo, we have developed a novel approach that permits the isolation and expansion of cells harboring expressing or silent retroviruses. MEL cells were infected with a Moloney murine leukemia virus encoding the green fluorescent protein (GFP), and single-copy, silent proviral clones were treated weekly with the histone deacetylase inhibitor trichostatin A or the DNA methylation inhibitor 5-azacytidine. Expression was monitored concurrently by flow cytometry, allowing for repeated phenotypic analysis over time, and proviral methylation was determined by Southern blotting and bisulfite methylation mapping. Shortly after infection, proviral expression was inducible and the reporter gene and proviral enhancer showed a low density of methylation. Over time, the efficacy of drug induction diminished, coincident with the accumulation of methyl-CpGs across the provirus. Bisulfite analysis of cells in which 5-azacytidine treatment induced GFP expression revealed measurable but incomplete demethylation of the provirus. Repression could be overcome in late-passage clones only by pretreatment with 5-azacytidine followed by trichostatin A, suggesting that partial demethylation reestablishes the trichostatin-inducible state. These experiments reveal the presence of a silencing mechanism which acts on densely methylated DNA and appears to function independently of histone deacetylase activity.

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