Disease relevance of Hdac1

• We investigated the role of a histone deacetylase (HDAC)-dependent mechanism in the transcriptional repression of cx43 in a panel of prostate cancer cells [1].
• In contrast the HDAC1 gene in other mouse strains such as C57B16, C3H/An and C-RY lacks the retrovirus [2].
• In the genome of 129SV mice the largest intervening sequence of the HDAC1 gene, intron 3, harbors a complete copy of the endogenous retrovirus MuERV-L [2].
• Recently, the inhibition of histone deacetylase (HDAC) enzymes has attracted attention in the oncologic community as a new therapeutic opportunity for hematologic and solid tumors including non-small cell lung cancer (NSCLC) [3].
• Histone deacetylase (HDAC) inhibitors alleviate neurological phenotypes in fly and mouse models of polyQ disease, although the therapeutic effect is limited by the toxicity of these compounds [4].

Psychiatry related information on Hdac1

• Phosphodiesterase 4 and histone deacetylase inhibitors, which can enhance CRE-dependent gene expression, have been shown to ameliorate memory deficits and neurodegeneration in animal models [5].
• Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease [6].
• The association of the histone deacetylase (HDAC) inhibitor valproate (VPA) with atypical antipsychotics has become a frequent treatment strategy for schizophrenia and bipolar disorder [7].

High impact information on Hdac1

• We show that m-Bop is a histone deacetylase-dependent transcriptional repressor [8].
• NoRC mediates rDNA silencing by recruiting DNA methyltransferase and histone deacetylase activity to the rDNA promoter, thus establishing structural characteristics of heterochromatin such as DNA methylation, histone hypoacetylation and methylation of the Lys9 residue of histone H3 [9].
• We suggest that the process of DNA methylation, mediated by Dnmt1, may depend on or generate an altered chromatin state via histone deacetylase activity [10].
• Using specific antibodies, however, we find here that MBD2 in HeLa cells is associated with histone deacetylase (HDAC) in the MeCP1 repressor complex [11].
• These two proteins locally influence chromatin structure: Rb recruits a histone deacetylase, whereas CBP is a histone acetyltransferase [12].

Chemical compound and disease context of Hdac1

• PURPOSE: To assess the antitumor effects of a novel phenylbutyrate-derived histone deacetylase (HDAC) inhibitor, (S)-HDAC-42, vis-à-vis suberoylanilide hydroxamic acid (SAHA) in in vitro and in vivo models of human prostate cancer [13].
• Effects of histone deacetylase inhibitors on estradiol-induced proliferation and hyperplasia formation in the mouse uterus [14].
• In this study, the in vivo efficiency of two HDACs, sodium butyrate and tributyrin, on prostate cancer growth inhibition were investigated [15].
• To gain insight into the role of histone acetylation in retinoid-dependent transcription, we studied the effects of trichostatin A (TSA), a specific inhibitor of histone deacetylase, on P19 embryonal carcinoma cells [16].
• Histone deacetylase inhibitors reduce polyglutamine toxicity [17].

Biological context of Hdac1

• Transcription and gene expression analyses of HSC clone embryos revealed that they initiated zygotic gene activation (ZGA) at the appropriate timing, but failed to activate five out of six important embryonic genes examined, including Hdac1 (encoding histone deacetylase 1), a key regulator of subsequent ZGA [18].
• We were interested in identifying interaction partners of histone deacetylase 1 (HDAC1) that might be involved in conferring target or substrate specificity [19].
• In the present study, we provide evidence that trichostatin A (TSA), a specific inhibitor of histone deacetylase, can elevate H3 and H4 acetylation and p21WAF1 expression in NIH3T3 cells at first [20].
• Trichostatin A, an inhibitor of histone deacetylase, inhibits smooth muscle cell proliferation via induction of p21(WAF1) [21].
• The HDAC1 gene comprises 14 exons ranging from 49 to 539 bp [2].

Anatomical context of Hdac1

• Upon exposure to sodium butyrate, a histone deacetylase inhibitor, cultured LEPCs differentiate and express functional hepatocyte markers albumin, tryptophan 2, 3-dioxygenase and alcohol dehydrogenase [22].
• LPS regulates proinflammatory gene expression in macrophages by altering histone deacetylase expression [23].
• Histone deacetylase (HDAC) inhibitors have shown utility in controlling proliferation in a wide range of tumor cell lines, possibly by inducing the expression of p21(WAF1) [21].
• PPARgamma and RB were shown to coimmunoprecipitate, and this PPARgamma-RB complex also contains the histone deacetylase HDAC3, thereby attenuating PPARgamma's capacity to drive gene expression and adipocyte differentiation [24].
• Our goal was to investigate the effect of trichostatin A (TSA), a specific and potent HDAC inhibitor, on the proliferation of vascular smooth muscle cells (VSMCs) isolated from rat thoracic aorta [21].

Associations of Hdac1 with chemical compounds

• Association of histone deacetylase 1 (HDAC1) with the promoter decreased after treatment with TSA or 5-AzaC and was abolished after treatment with both inhibitors [25].
• TSA suppressed the HDAC activity of VSMCs in a dose-dependent manner and inhibited VSMC proliferation as demonstrated by cell number counting and the degree of [3H] thymidine incorporation [21].
• Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor [26].
• Combined effects of novel tyrosine kinase inhibitor AMN107 and histone deacetylase inhibitor LBH589 against Bcr-Abl-expressing human leukemia cells [27].
• However, such resistance was readily reversed when Apo2L/TRAIL was used in combination with clinically relevant chemotherapeutic drugs, including taxol, etoposide, doxorubicin, cisplatin, or the histone deacetylase inhibitor suberoylanilide hydroxamic acid [28].

Physical interactions of Hdac1

• Association of the mSin3A-histone deacetylase 1/2 corepressor complex with the mouse steroidogenic acute regulatory protein gene [29].
• These results show that Ski is a component of the HDAC complex and that Ski is required for the transcriptional repression mediated by this complex [26].
• TZDs trigger the dismissal of corepressor histone deacetylase (HDAC) complexes and the recruitment of coactivators to the GyK gene [30].
• In this study, we demonstrate that pRb2/p130 binds to HDAC1 [31].

Regulatory relationships of Hdac1

• Histone deacetylase inhibitor-induced expression of p21WAF1 is p53 independent [20].
• Both Sp1 and Sp3 are responsible for p21waf1 promoter activity induced by histone deacetylase inhibitor in NIH3T3 cells [20].
• Together, these results demonstrate that histone deacetylase inhibitor VPA suppresses adiponectin gene expression in mature adipocytes [32].
• Stra13 expression is transcriptionally repressed and maintained at a low level in cells through a negative autoregulatory mechanism that is brought about by its interaction with the corepressor histone deacetylase (HDAC1) [33].
• CONCLUSIONS: These studies show that histone deacetylase activity regulates osteoblast differentiation and bone formation at least in part by enhancing Runx2-dependent transcriptional activation [34].

Other interactions of Hdac1

• Both HD1 protein levels and total histone deacetylase activity increased upon interleukin-2 stimulation of resting B6.1 cells [35].
• Information concerning the genomic organization and promoter of HDAC2 will be useful in studies of the regulation of histone deacetylase activities, which in turn are important in studies of the regulation of transcriptional repression in mammalian cells [36].
• Furthermore, trichostatin A, a potent histone deacetylase inhibitor, impaired TEL-dependent repression of the stromelysin-1 promoter [37].
• The involvement of c-Ski in the HDAC complex indicates that the function of the HDAC complex is important for oncogenesis [26].
• To elucidate the role of focal adhesion kinase (pp125FAK) in transformation, its phosphorylation in transformed fibroblasts was compared with that of detransformed fibroblasts induced by a histone deacetylase inhibitor, trichostatin A (TSA) [38].

Analytical, diagnostic and therapeutic context of Hdac1

• At least four small-molecule histone deacetylase inhibitors are currently in clinical trials for the treatment of cancer [39].
• METHODS: The impact of Trichostatin A (TSA), an inhibitor of HDAC, on exogenous and endogenous cx43 gene transcription was examined by the luciferase assay, Northern blot, nuclear run-on, Western blot, and chromatin immunoprecipitation assays [1].
• Using chromatin immunoprecipitation assays, we show that histone deacetylase 1 (HDAC1) is associated with the endogenous mitochondrial HMG-CoA synthase promoter and that TSA induction correlates with hyperacetylation of H4 histone associated with the 5' flanking region of the gene [40].
• Molecular cloning and characterization of the mouse histone deacetylase 1 gene: integration of a retrovirus in 129SV mice [2].
• In vivo biological activity of the histone deacetylase inhibitor LAQ824 is detectable with 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography [41].

References