scholarly journals Significance of DNA methyltransferase-1 and histone deacetylase-1 in pancreatic cancer

2009 ◽  
Vol 21 (6) ◽  
Author(s):  
Li
Keyword(s):  
Pancreatic Cancer ◽  
Histone Deacetylase ◽  
Dna Methyltransferase ◽  
Dna Methyltransferase 1 ◽  
Histone Deacetylase 1 ◽  
Methyltransferase 1

scholarly journals Chromium Cross-Links Histone Deacetylase 1-DNA Methyltransferase 1 Complexes to Chromatin, Inhibiting Histone-Remodeling Marks Critical for Transcriptional Activation

2007 ◽  
Vol 27 (20) ◽  
pp. 7089-7101 ◽  
Author(s):  
Michael Schnekenburger ◽  
Glenn Talaska ◽  
Alvaro Puga
Keyword(s):  
Gene Expression ◽  
Histone Deacetylase ◽  
Dna Methyltransferase ◽  
Epigenetic Modification ◽  
Dna Methyltransferase 1 ◽  
Transcriptional Responses ◽  
Histone Deacetylase 1 ◽  
Environmental Agents ◽  
Cross Links ◽  
Methyltransferase 1

ABSTRACT Transcriptional regulation of gene expression requires posttranslational modification of histone proteins, which, in concert with chromatin-remodeling factors, modulate chromatin structure. Exposure to environmental agents may interfere with specific histone modifications and derail normal patterns of gene expression. To test this hypothesis, we coexposed cells to binary mixtures of benzo[a]pyrene (B[a]P), an environmental procarcinogen that activates Cyp1a1 transcriptional responses mediated by the aryl hydrocarbon receptor (AHR), and chromium, a carcinogenic heavy metal that represses B[a]P-inducible AHR-mediated gene expression. We show that chromium cross-links histone deacetylase 1-DNA methyltransferase 1 (HDAC1-DNMT1) complexes to Cyp1a1 promoter chromatin and inhibits histone marks induced by AHR-mediated gene transactivation, including phosphorylation of histone H3 Ser-10, trimethylation of H3 Lys-4, and various acetylation marks in histones H3 and H4. These changes inhibit RNA polymerase II recruitment without affecting the kinetics of AHR DNA binding. HDAC1 and DNMT1 inhibitors or depletion of HDAC1 or DNMT1 with siRNAs blocks chromium-induced transcriptional repression by decreasing the interaction of these proteins with the Cyp1a1 promoter and allowing histone acetylation to proceed. By inhibiting Cyp1a1 expression, chromium stimulates the formation of B[a]P DNA adducts. Epigenetic modification of gene expression patterns may be a key element of the developmental and carcinogenic outcomes of exposure to chromium and to other environmental agents.

scholarly journals DNA-Methyltransferase 1 Induces Dedifferentiation of Pancreatic Cancer Cells through Silencing of Krüppel-Like Factor 4 Expression

2017 ◽  
Vol 23 (18) ◽  
pp. 5585-5597 ◽  
Author(s):  
Victoria K. Xie ◽  
Zhiwei Li ◽  
Yongmin Yan ◽  
Zhiliang Jia ◽  
Xiangsheng Zuo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Dna Methyltransferase ◽  
Dna Methyltransferase 1 ◽  
Pancreatic Cancer Cells ◽  
Methyltransferase 1

scholarly journals 8a, a New Acridine Antiproliferative and Pro-Apoptotic Agent Targeting HDAC1/DNMT1

2021 ◽  
Vol 22 (11) ◽  
pp. 5516
Author(s):  
Qiting Zhang ◽  
Ziyan Wang ◽  
Xinyuan Chen ◽  
Haoxiang Qiu ◽  
Yifan Gu ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Dna Methyltransferase ◽  
Hdac Inhibitors ◽  
Mitochondrial Pathway ◽  
Epigenetic Therapy ◽  
Protein Interaction Data ◽  
Dependent Manner ◽  
Histone Deacetylase 1 ◽  
Histiocytic Lymphoma ◽  
Dose Dependent

Epigenetic therapy using histone deacetylase (HDAC) inhibitors has become an attractive project in new drug development. However, DNA methylation and histone acetylation are important epigenetic ways to regulate the occurrence and development of leukemia. Given previous studies, N-(2-aminophenyl)benzamide acridine (8a), as a histone deacetylase 1 (HDAC1) inhibitor, induces apoptosis and shows significant anti-proliferative activity against histiocytic lymphoma U937 cells. HDAC1 plays a role in the nucleus, which we confirmed by finding that 8a entered the nucleus. Subsequently, we verified that 8a mainly passes through the endogenous (mitochondrial) pathway to induce cell apoptosis. From the protein interaction data, we found that 8a also affected the expression of DNA methyltransferase 1 (DNMT1). Therefore, an experiment was performed to assess the binding of 8a to DNMT1 at the molecular and cellular levels. We found that the binding strength of 8a to DNMT1 enhanced in a dose-dependent manner. Additionally, 8a inhibits the expression of DNMT1 mRNA and its protein. These findings suggested that the anti-proliferative and pro-apoptotic activities of 8a against leukemia cells were achieved by targeting HDAC1 and DNMT1.

scholarly journals DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria

2011 ◽  
Vol 108 (9) ◽  
pp. 3630-3635 ◽  
Author(s):  
Lisa S. Shock ◽  
Prashant V. Thakkar ◽  
Erica J. Peterson ◽  
Richard G. Moran ◽  
Shirley M. Taylor
Keyword(s):  
Dna Methyltransferase ◽  
Cytosine Methylation ◽  
Dna Methyltransferase 1 ◽  
Mammalian Mitochondria ◽  
Methyltransferase 1
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