scholarly journals The Interplay between Toxic and Essential Metals for Their Uptake and Translocation Is Likely Governed by DNA Methylation and Histone Deacetylation in Maize

2020 ◽  
Vol 21 (18) ◽  
pp. 6959
Author(s):  
Sarfraz Shafiq ◽  
Asim Ali ◽  
Yasar Sajjad ◽  
Qudsia Zeb ◽  
Muhammad Shahzad ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Contaminated Soils ◽  
Histone Deacetylases ◽  
Dna Methyltransferases ◽  
Histone Deacetylation ◽  
Growth And Yield ◽  
Aerial Parts ◽  
Maize Plants ◽  
Iron Regulated Transporter ◽  
Zip Transporters

The persistent nature of lead (Pb) and cadmium (Cd) in the environment severely affects plant growth and yield. Conversely, plants acquire zinc (Zn) from the soil for their vital physiological and biochemical functions. However, the interplay and coordination between essential and toxic metals for their uptake and translocation and the putative underlying epigenetic mechanisms have not yet been investigated in maize. Here, we report that the presence of Zn facilitates the accumulation and transport of Pb and Cd in the aerial parts of the maize plants. Moreover, the Zn, Pb, and Cd interplay specifically interferes with the uptake and translocation of other divalent metals, such as calcium and magnesium. Zn, Pb, and Cd, individually and in combinations, differentially regulate the expression of DNA methyltransferases, thus alter the DNA methylation levels at the promoter of Zinc-regulated transporters, Iron-regulated transporter-like Protein (ZIP) genes to regulate their expression. Furthermore, the expression of histone deacetylases (HDACs) varies greatly in response to individual and combined metals, and HDACs expression showed a negative correlation with ZIP transporters. Our study highlights the implication of DNA methylation and histone acetylation in regulating the metal stress tolerance dynamics through Zn transporters and warns against the excessive use of Zn fertilizers in metal contaminated soils.

P.2.e.017 DNA methylation is selectively altered in bipolar disorder and linked to DNA methyltransferases and histone deacetylases mRNAs levels

2012 ◽  
Vol 22 ◽  
pp. S285-S286
Author(s):  
C. D'Addario ◽  
B. Dell'Osso ◽  
A. Di Francesco ◽  
M.C. Palazzo ◽  
B. Benatti ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bipolar Disorder ◽  
Histone Deacetylases ◽  
Dna Methyltransferases

Expression of ATRA Inducible RARα2 Isoform Is Deregulated in AML.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1204-1204
Author(s):  
Annegret Glasow ◽  
Angela Barrett ◽  
Rajeev Gupta ◽  
David Grimwade ◽  
Marieke von Lindern ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Retinoic Acid ◽  
Cell Lines ◽  
Histone Deacetylases ◽  
Target Genes ◽  
Retinoic Acid Receptor ◽  
Cell Types ◽  
Dna Methyltransferases ◽  
Protein Isoforms ◽  
Epigenetic Changes

Abstract Retinoids exert a variety of effects on both normal and malignant hematopoietic cells. To date, three different retinoic acid receptor (RAR) and retinoid X receptor (RXR) genes have been characterized, each encoding multiple N-terminal protein isoforms. RXRs serve as co-regulators for RARs, and many other nuclear receptors integrating different signalling pathways. All-trans-retinoic acid (ATRA) signaling pathway is of critical importance for optimal myelomonocytic differentiation and its disruption by translocations of the RARα gene leads to acute promyelocytic leukemia (APL). APL associated fusion oncoproteins, such as PML-RARα and PLZF-RARα, function through recruitment of histone deacetylases (HDACs) and DNA methyltransferases (DNMTs), thus promoting an inactive chromatin state and leading to repression of RARα target genes. Recently, we demonstrated that up-regulation of RARα2 expression by ATRA directly correlates with differentiation of APL and non-APL AML cells and that RARα2 transcription is silenced by DNA methylation in AML cell lines. Using primary AML samples as well as normal cord and peripheral blood derived cells representing different stages of myelomonocytic development we now show that expression of RARα2 increases with maturation of hematopietic cells. Expression of RARα1 on the other hand, which is transcribed from a distinct promoter, remains relatively constant throughout the different stages of myelomonocytic development. The levels of RARα1 expression in various primary AML cell types appear to be similar to those found in normal hematopietic cells. Consistent with data derived from AML cell lines, however, the RARα2 isoform is poorly expressed in all samples. Compared with CD34+/CD133+ or CD34+ progenitors, and more mature CD33+ myeloid cells, RARα2 is expressed at much lower levels in a variety of primary AML cells and its expression is not effectively induced by myelomonocytic growth factors and/or ATRA. Negatively acting epigenetic changes, such as DNA methylation, appear to be responsible for deregulated expression of RARα2 in AML cells, although their pattern and extent differs significantly between AML cell lines and primary AML samples. Taken together our data suggest that agents, which revert negatively acting epigenetic changes may restore expression of the RARα2 isoform in AML cells and render them more responsive to ATRA as well as other differentiation inducers.

scholarly journals LSH Cooperates with DNA Methyltransferases To Repress Transcription

2007 ◽  
Vol 28 (1) ◽  
pp. 215-226 ◽  
Author(s):  
Kevin Myant ◽  
Irina Stancheva
Keyword(s):  
Dna Methylation ◽  
Chromatin Remodeling ◽  
Transcriptional Repression ◽  
Histone Deacetylases ◽  
Mammalian Cells ◽  
Dna Methyltransferase ◽  
Dna Methyltransferases ◽  
Large Protein ◽  
Large Protein Complex ◽  
Nuclear Extracts

ABSTRACT LSH, a protein related to the SNF2 family of chromatin-remodeling ATPases, is required for efficient DNA methylation in mammals. How LSH functions to support DNA methylation and whether it associates with a large protein complex containing DNA methyltransferase (DNMT) enzymes is currently unclear. Here we show that, unlike many other chromatin-remodeling ATPases, native LSH is present mostly as a monomeric protein in nuclear extracts of mammalian cells and cannot be detected in a large multisubunit complex. However, when targeted to a promoter of a reporter gene, LSH acts as an efficient transcriptional repressor. Using this as an assay to identify proteins that are required for LSH-mediated repression we found that LSH cooperates with the DNMTs DNMT1 and DNMT3B and with the histone deacetylases (HDACs) HDAC1 and HDAC2 to silence transcription. We show that transcriptional repression by LSH and interactions with HDACs are lost in DNMT1 and DNMT3B knockout cells but that the enzymatic activities of DNMTs are not required for LSH-mediated silencing. Our data suggest that LSH serves as a recruiting factor for DNMTs and HDACs to establish transcriptionally repressive chromatin which is perhaps further stabilized by DNA methylation at targeted loci.

scholarly journals Immunological Effects of Epigenetic Modifiers

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1911 ◽  
Author(s):  
Lucillia Bezu ◽  
Alejandra Wu Chuang ◽  
Peng Liu ◽  
Guido Kroemer ◽  
Oliver Kepp
Keyword(s):  
Dna Methylation ◽  
Histone Deacetylases ◽  
Methylation Status ◽  
Dna Methyltransferases ◽  
Cancer Hallmarks ◽  
Epigenetic Modifiers ◽  
Oncogenic Pathways ◽  
Immunotherapeutic Strategy ◽  
Immunological Effects ◽  
Molecular Patterns

Epigenetic alterations are associated with major pathologies including cancer. Epigenetic dysregulation, such as aberrant histone acetylation, altered DNA methylation, or modified chromatin organization, contribute to oncogenesis by inactivating tumor suppressor genes and activating oncogenic pathways. Targeting epigenetic cancer hallmarks can be harnessed as an immunotherapeutic strategy, exemplified by the use of pharmacological inhibitors of DNA methyltransferases (DNMT) and histone deacetylases (HDAC) that can result in the release from the tumor of danger-associated molecular patterns (DAMPs) on one hand and can (re-)activate the expression of tumor-associated antigens on the other hand. This finding suggests that epigenetic modifiers and more specifically the DNA methylation status may change the interaction of chromatin with chaperon proteins including HMGB1, thereby contributing to the antitumor immune response. In this review, we detail how epigenetic modifiers can be used for stimulating therapeutically relevant anticancer immunity when used as stand-alone treatments or in combination with established immunotherapies.

scholarly journals Epigenetic determinants in rheumatoid arthritis: the influence of DNA methylation and histone modifications

2017 ◽  
Vol 71 (0) ◽  
pp. 0-0
Author(s):  
Bogdan Kolarz ◽  
Maria Majdan
Keyword(s):  
Rheumatoid Arthritis ◽  
Dna Methylation ◽  
Histone Modifications ◽  
Histone Deacetylases ◽  
Dna Methyltransferases ◽  
Epigenetic Mechanisms ◽  
Epigenetic Changes ◽  
Genetic Changes ◽  
Post Translational Modifications ◽  
Methylation Of Dna

Epigenetics is a field of science which describes external and environmental modifications to DNA without altering their primary sequences of nucleotides. Contrary to genetic changes, epigenetic modifications are reversible. The epigenetic changes appear as a result of the influence of external factors, such as diet or stress. Epigenetic mechanisms alter the accessibility of DNA by methylation of DNA or post-translational modifications of histones (acetylation, methylation, phosphorylation, ubiquitinqation). The extent of DNA methylation depends on the balance between DNA methyltransferases and demethylases. The main histone modifications are stimulated by K-acetyltransferases, histone deacetylases, K-metyltransferases and K-demethylases. There is proof that environmental modifications of this enzymes regulate immunological processes including autoimmunity in rheumatoid arthritis (RA). In this work we present epigenetic mechanisms involved in RA pathogenesis and a range of research presenting the possible impact of its modification in RA patients.

scholarly journals Influence of Benzo(a)pyrene on Different Epigenetic Processes

2021 ◽  
Vol 22 (24) ◽  
pp. 13453
Author(s):  
Bożena Bukowska ◽  
Paulina Sicińska
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Histone Deacetylases ◽  
Polyaromatic Hydrocarbons ◽  
Methylation Status ◽  
Underlying Mechanism ◽  
Epidemiological Studies ◽  
Dna Methyltransferases ◽  
Epigenetic Changes ◽  
Marine Medaka

Epigenetic changes constitute one of the processes that is involved in the mechanisms of carcinogenicity. They include dysregulation of DNA methylation processes, disruption of post-translational patterns of histone modifications, and changes in the composition and/or organization of chromatin. Benzo(a)pyrene (BaP) influences DNA methylation and, depending on its concentrations, as well as the type of cell, tissue and organism it causes hypomethylation or hypermethylation. Moreover, the exposure to polyaromatic hydrocarbons (PAHs), including BaP in tobacco smoke results in an altered methylation status of the offsprings. Researches have indicated a potential relationship between toxicity of BaP and deregulation of the biotin homeostasis pathway that plays an important role in the process of carcinogenesis. Animal studies have shown that parental-induced BaP toxicity can be passed on to the F1 generation as studied on marine medaka (Oryzias melastigma), and the underlying mechanism is likely related to a disturbance in the circadian rhythm. In addition, ancestral exposure of fish to BaP may cause intergenerational osteotoxicity in non-exposed F3 offsprings. Epidemiological studies of lung cancer have indicated that exposure to BaP is associated with changes in methylation levels at 15 CpG; therefore, changes in DNA methylation may be considered as potential mediators of BaP-induced lung cancer. The mechanism of epigenetic changes induced by BaP are mainly due to the formation of CpG-BPDE adducts, between metabolite of BaP—BPDE and CpG, which leads to changes in the level of 5-methylcytosine. BaP also acts through inhibition of DNA methyltransferases activity, as well as by increasing histone deacetylases HDACs, i.e., HDAC2 and HDAC3 activity. The aim of this review is to discuss the mechanism of the epigenetic action of BaP on the basis of the latest publications.

Epigenetic Targets and their Inhibitors in Cancer Therapy

2019 ◽  
Vol 18 (28) ◽  
pp. 2395-2419 ◽  
Author(s):  
Le Zhao ◽  
Yong-Tao Duan ◽  
Ping Lu ◽  
Zhi-Juan Zhang ◽  
Xiao-Ke Zheng ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cancer Therapy ◽  
Histone Deacetylases ◽  
Epigenetic Modification ◽  
Genetic Mutation ◽  
Dna Methyltransferases ◽  
Epigenetic Drugs ◽  
Histone Methyltransferases ◽  
Dna Nucleotide Sequence ◽  
Made In

Epigenetics is defined as the stable and heritable alternations in gene expression without changing the DNA nucleotide sequence. The initiation and progression of cancer result from not only genetic mutation, but also aberrant epigenetic regulation, such as DNA methylation and histones acetylation. Although Genetic alternations cannot be reversed, epigenetic modification is a dynamic and reversible process. Over the past few decades, much progress has been made in the research of epigenetic medications and a variety of drugs have been developed targeting at epigenetic regulatory proteins, which are capable of restoring malignant cancer cells to the normal state. The epigenetic drugs currently approved for cancer treatment mainly target at DNA methylation and histones acetylation. In addition, there are a great many epigenetic drugs in clinical trials for cancer therapy, such as inhibitors of DNA methyltransferases, histone deacetylases, histone methyltransferases, lysine specific demethylases, and BET (bromodomain and extra-terminal domain) family proteins. We will discuss the latest developments of these inhibitors and their applications in cancer therapy.

scholarly journals 236 SPATIAL GENE EXPRESSION PATTERNS OF Dnmt1, Dnmt3a, AND Hdac2 IN PREIMPLANTATION EMBRYOS

2005 ◽  
Vol 17 (2) ◽  
pp. 268
Author(s):  
C. Wrenzycki ◽  
D. Herrmann ◽  
A. Lucas-Hahn ◽  
K. Korsawe ◽  
E. Lemme ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Relative Abundance ◽  
Expression Patterns ◽  
Dna Methyltransferases ◽  
Histone Deacetylation ◽  
Preimplantation Embryos ◽  
Differential Staining ◽  
Rt Pcr

In mammals, DNA methylation and the modification of histones account for the major epigenetic alterations. Usually DNA methylation is associated with transcriptional silencing, which is catalyzed by two important classes of DNA methyltransferases. DNA methyltransferase 1 (Dnmt1), a maintenance enzyme, methylates hemi-methylated DNA after DNA replication. Dnmt3a and Dnmt3b are required for de novo methylation in vivo and for establishing new DNA methylation marks during development. In addition to DNA methylation, post-translational modifications of the amino termini of core histones are thought to affect the expression or repression of transcription. Histone deacetylation catalyzsed by histone deacetylases (Hdac) often results in transcriptional repression. Perturbated epigenetic reprogramming of the genome is a likely cause of developmental abnormalities and epigenetic diseases introduced by assisted reproduction technologies. The objective of the present study was to determine the relative abundance of Dnmt1, Dnmt3a, and Hdac2 transcripts in ICM and TE cells of pre-implantation bovine embryos of different origin. Embryos were generated with standard protocols of in vitro production (IVP) and parthenogenetic activation using SOF medium supplemented with BSA (SOF d7/d8, Parth d7/d8) or TCM medium supplemented with estrus cow serum (TCM d7/d8; Wrenzycki et al. 2001 Hum. Reprod. 16, 893–901; Wrenzycki et al. 2002 Biol. Reprod. 66, 127–134). Expanded blastocysts were collected at Days 7 and Day 8 (d7/d8) of culture (Day 0 = IVF). In vivo-generated blastocysts collected from superovulated animals were included as controls (Wrenzycki et al. 1996 J. Reprod. Fert. 108, 17–24). A highly sensitive RT-PCR assay (Wrenzycki et al. 2003 Biol. Reprod. 68, 2073–2080) was used to determine the relative abundance (RA) of gene transcripts in isolated ICM and TE cells. The allocation of ICM and TE cells was analyzed using a differential staining technique (Eckert and Niemann 1998 Mol. Hum. Reprod. 4, 957–965) to calculate the RA of each transcript on a per cell basis. RT-PCR assays were repeated at least six times. Significant differences in the RA of Dnmt1 (In vivo, TCM d7, Parth d7/d8, SOF d8), Dnmt3a (In vivo, SOF d7), and Hdac2 (TCM d7) transcripts were detected between ICM and TE cells. No differences were detected for all transcripts in ICM cells of embryos collected at either Day 7 or Day 8. In TE cells, the RA of Dnmt1 transcripts was significantly reduced or increased in embryos generated in SOF or TCM medium at Day 7, respectively, and the RA of Hdac2 transcripts was significantly higher in embryos generated in TCM medium at Day 8. These results suggest that in vitro culture alters the spatial expression pattern of genes related to epigenetic modifications in the cell lineages critical for a normal embryonic and fetal development. This work was supported by the Deutsche Forschungsgemeinschaft (DFG Ni 256/18-1).

scholarly journals Neuroblastoma and the epigenome

2021 ◽  
Author(s):  
Irfete S. Fetahu ◽  
Sabine Taschner-Mandl
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Disease Diagnosis ◽  
Dna Methyltransferases ◽  
Epigenetic Alterations ◽  
Aberrant Expression ◽  
Tet Proteins ◽  
Relative Paucity ◽  
Underlying Causes ◽  
Aberrant Dna Methylation

AbstractNeuroblastoma (NB) is a pediatric cancer of the sympathetic nervous system and one of the most common solid tumors in infancy. Amplification of MYCN, copy number alterations, numerical and segmental chromosomal aberrations, mutations, and rearrangements on a handful of genes, such as ALK, ATRX, TP53, RAS/MAPK pathway genes, and TERT, are attributed as underlying causes that give rise to NB. However, the heterogeneous nature of the disease—along with the relative paucity of recurrent somatic mutations—reinforces the need to understand the interplay of genetic factors and epigenetic alterations in the context of NB. Epigenetic mechanisms tightly control gene expression, embryogenesis, imprinting, chromosomal stability, and tumorigenesis, thereby playing a pivotal role in physio- and pathological settings. The main epigenetic alterations include aberrant DNA methylation, disrupted patterns of posttranslational histone modifications, alterations in chromatin composition and/or architecture, and aberrant expression of non-coding RNAs. DNA methylation and demethylation are mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins, respectively, while histone modifications are coordinated by histone acetyltransferases and deacetylases (HATs, HDACs), and histone methyltransferases and demethylases (HMTs, HDMs). This article focuses predominately on the crosstalk between the epigenome and NB, and the implications it has on disease diagnosis and treatment.

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