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 EGCG Prevents High Fat Diet-Induced Changes in Gut Microbiota, Decreases of DNA Strand Breaks, and Changes in Expression and DNA Methylation ofDnmt1andMLH1in C57BL/6J Male Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Marlene Remely ◽  
Franziska Ferk ◽  
Sonja Sterneder ◽  
Tahereh Setayesh ◽  
Sylvia Roth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Dna Damage ◽  
Gut Microbiota ◽  
High Fat Diet ◽  
Dna Methyltransferase ◽  
Dna Methyltransferase 1 ◽  
Male Mice ◽  
High Fat ◽  
Methyltransferase 1

Obesity as a multifactorial disorder involves low-grade inflammation, increased reactive oxygen species incidence, gut microbiota aberrations, and epigenetic consequences. Thus, prevention and therapies with epigenetic active antioxidants, (-)-Epigallocatechin-3-gallate (EGCG), are of increasing interest. DNA damage, DNA methylation and gene expression ofDNA methyltransferase 1,interleukin 6, andMutL homologue 1were analyzed in C57BL/6J male mice fed a high-fat diet (HFD) or a control diet (CD) with and without EGCG supplementation. Gut microbiota was analyzed with quantitative real-time polymerase chain reaction. An induction of DNA damage was observed, as a consequence of HFD-feeding, whereas EGCG supplementation decreased DNA damage. HFD-feeding induced a higher inflammatory status. Supplementation reversed these effects, resulting in tissue specific gene expression and methylation patterns ofDNA methyltransferase 1andMutL homologue 1. HFD feeding caused a significant lower bacterial abundance. TheFirmicutes/Bacteroidetesratio is significantly lower in HFD + EGCG but higher in CD + EGCG compared to control groups. The results demonstrate the impact of EGCG on the one hand on gut microbiota which together with dietary components affects host health. On the other hand effects may derive from antioxidative activities as well as epigenetic modifications observed on CpG methylation but also likely to include other epigenetic elements.

scholarly journals Gene Expression Pattern and Downregulation of DNA Methyltransferase 1 Using siRNA in Porcine Somatic Cells

2009 ◽  
Vol 14 (5) ◽  
pp. 251-263 ◽  
Author(s):  
ANGELICA M. GIRALDO ◽  
TODD D. VAUGHT ◽  
LIMIN FU ◽  
ALISON J. DUNCAN ◽  
AMY M. VANCE ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
Dna Methyltransferase ◽  
Somatic Cells ◽  
Gene Expression Pattern ◽  
Dna Methyltransferase 1 ◽  
Methyltransferase 1

scholarly journals Effect of 5'-fluoro-2'-deoxycytidine, 5-azacytidine, and 5-aza-2'–deoxycytidine on DNA Methyltransferase 1, CIP/KIP Family, and INK4a/ARF in Colon Cancer HCT-116 Cell Line

2022 ◽  
Vol 14 (12) ◽  
Author(s):  
Masumeh Sanaei ◽  
Fraidoon Kavoosi
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Growth ◽  
Cell Line ◽  
Dna Methyltransferase ◽  
Negative Regulator ◽  
Dna Methyltransferase 1 ◽  
Hct 116 ◽  
Methyltransferase 1

Background: Cyclin-dependent kinase inhibitors (CKIs) are the negative regulator of cell cycle progression, which inhibits cyclin-cdk complexes, resulting in cell cycle arrest. Recently, we evaluated the effect of 5-Aza-CdR on DNMT1 gene expression in the WCH-17 hepatocellular carcinoma (HCC) cell line. Objectives: The current study was designed to analyze the effects of 5-aza-2'–deoxycytidine (5-Aza-CdR, decitabine), 5-azacytidine (5-AzaC, vidaza), and 5'-fluoro-2'-deoxycytidine (FdCyd) on INK4a/ARF, CIP/KIP, and DNA methyltransferase 1 gene expression, apoptosis induction, and cell growth inhibition in colon cancer HCT-116 cell line. Methods: The colon cancer HCT-116 cell line was treated with 5-azaC, 5-Aza-CdR, and FdCyd at 24 and 48h. To determine colon cancer HCT-116 cell viability, cell apoptosis, and the relative expression level of the INK4a/ARF, CIP/KIP, and DNA methyltransferase 1 genes, MTT assay, flow cytometry, and qRT-PCR were done, respectively. Results: 5-azaC, 5-Aza-CdR, and FdCyd significantly inhibited colon cancer HCT-116 cell growth and induced apoptosis. Besides, they significantly increased CIP/KIP (p21CIP1, p27KIP1, and p57KIP2) and INK4 (p14ARF, p15INK4b, and p16INK4a) and decreased DNMT1 gene expression. Besides, minimal and maximal apoptosis were seen in the groups treated with FdCyd and 5-Aza-CdR, respectively. The IC50 for CAF for FdCyd was 1.72 ± 0.23 and 1.63 ± 0.21μM at 24 and 48h, respectively. The IC50 for CAF for 5-AzaC was 2.18 ± 0.33 and 1.98 ± 0.29 μM at 24 and 48h, respectively. The IC50 for CAF for 5-Aza-CdR was 4.08 ± 0.61 and 3.18 ± 0.50 μM at 24 and 48h, respectively. Conclusions: The 5-azac, 5-Aza-CdR, and FdCyd can reactivate the INK4a/ARF and CIP/KIP families through inhibition of DNMT1 activity.

scholarly journals Loss of LSD1 (lysine-specific demethylase 1) suppresses growth and alters gene expression of human colon cancer cells in a p53- and DNMT1(DNA methyltransferase 1)-independent manner

2012 ◽  
Vol 449 (2) ◽  
pp. 459-468 ◽  
Author(s):  
Lihua Jin ◽  
Christin L. Hanigan ◽  
Yu Wu ◽  
Wei Wang ◽  
Ben Ho Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Dna Methyltransferase ◽  
Cpg Island ◽  
Colorectal Cancer Cell Line ◽  
Tumour Suppressor Genes ◽  
Dna Methyltransferase 1 ◽  
Lysine Specific Demethylase ◽  
Significant Difference ◽  
Methyltransferase 1

Epigenetic silencing of gene expression is important in cancer. Aberrant DNA CpG island hypermethylation and histone modifications are involved in the aberrant silencing of tumour-suppressor genes. LSD1 (lysine-specific demethylase 1) is a H3K4 (histone H3 Lys4) demethylase associated with gene repression and is overexpressed in multiple cancer types. LSD1 has also been implicated in targeting p53 and DNMT1 (DNA methyltransferase 1), with data suggesting that the demethylating activity of LSD1 on these proteins is necessary for their stabilization. To examine the role of LSD1 we generated LSD1 heterozygous (LSD1+/−) and homozygous (LSD1−/−) knockouts in the human colorectal cancer cell line HCT116. The deletion of LSD1 led to a reduced cell proliferation both in vitro and in vivo. Surprisingly, the knockout of LSD1 in HCT116 cells did not result in global increases in its histone substrate H3K4me2 (dimethyl-H3K4) or changes in the stability or function of p53 or DNMT1. However, there was a significant difference in gene expression between cells containing LSD1 and those null for LSD1. The results of the present study suggested that LSD1 is critical in the regulation of cell proliferation, but also indicated that LSD1 is not an absolute requirement for the stabilization of either p53 or DNMT1.

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