Reverting cholesterol auxotrophy of NS0 cells by altering epigenetic gene silencing

2006 ◽  
Vol 93 (4) ◽  
pp. 820-827 ◽  
Author(s):  
Gargi Seth ◽  
Mustafa Ozturk ◽  
Wei-Shou Hu
Keyword(s):  
Gene Silencing ◽  
Epigenetic Gene Silencing ◽  
Ns0 Cells ◽  
Cholesterol Auxotrophy

scholarly journals Nickel and Epigenetic Gene Silencing

Genes ◽  
2013 ◽  
Vol 4 (4) ◽  
pp. 583-595 ◽  
Author(s):  
Hong Sun ◽  
Magdy Shamy ◽  
Max Costa
Keyword(s):  
Gene Silencing ◽  
Epigenetic Gene Silencing

Potato Virus X Amplicons in Arabidopsis Mediate Genetic and Epigenetic Gene Silencing

2000 ◽  
Vol 12 (3) ◽  
pp. 369 ◽  
Author(s):  
Tamas Dalmay ◽  
Andrew Hamilton ◽  
Elisabeth Mueller ◽  
David C. Baulcombe
Keyword(s):  
Gene Silencing ◽  
Potato Virus ◽  
Potato Virus X ◽  
Epigenetic Gene Silencing

scholarly journals Modulations of SIR-nucleosome interactions of reconstructed yeast silent pre-heterochromatin by O-acetyl-ADP-ribose and magnesium

2017 ◽  
Vol 28 (3) ◽  
pp. 381-386 ◽  
Author(s):  
Shu-Yun Tung ◽  
Sue-Hong Wang ◽  
Sue-Ping Lee ◽  
Shu-Ping Tsai ◽  
Hsiao-Hsuian Shen ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Chromatin Condensation ◽  
Epigenetic Inheritance ◽  
Assembly System ◽  
Sir Proteins ◽  
Epigenetic Gene Silencing ◽  
In Vitro Assembly ◽  
The Individual

Yeast silent heterochromatin provides an excellent model with which to study epigenetic inheritance. Previously we developed an in vitro assembly system to demonstrate the formation of filament structures with requirements that mirror yeast epigenetic gene silencing in vivo. However, the properties of these filaments were not investigated in detail. Here we show that the assembly system requires Sir2, Sir3, Sir4, nucleosomes, and O-acetyl-ADP-ribose. We also demonstrate that all Sir proteins and nucleosomes are components of these filaments to prove that they are SIR-nucleosome filaments. Furthermore, we show that the individual localization patterns of Sir proteins on the SIR-nucleosome filament reflect those patterns on telomeres in vivo. In addition, we reveal that magnesium exists in the SIR-nucleosome filament, with a role similar to that for chromatin condensation. These results suggest that a small number of proteins and molecules are sufficient to mediate the formation of a minimal yeast silent pre-heterochromatin in vitro.

scholarly journals KAP-1 Corepressor Protein Interacts and Colocalizes with Heterochromatic and Euchromatic HP1 Proteins: a Potential Role for Krüppel-Associated Box–Zinc Finger Proteins in Heterochromatin-Mediated Gene Silencing

1999 ◽  
Vol 19 (6) ◽  
pp. 4366-4378 ◽  
Author(s):  
Robert F. Ryan ◽  
David C. Schultz ◽  
Kasirajan Ayyanathan ◽  
Prim B. Singh ◽  
Josh R. Friedman ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Zinc Finger ◽  
Transcriptional Repression ◽  
Zinc Finger Proteins ◽  
Centromeric Heterochromatin ◽  
Interphase Nuclei ◽  
Epigenetic Gene Silencing ◽  
Associated Proteins

ABSTRACT Krüppel-associated box (KRAB) domains are present in approximately one-third of all human zinc finger proteins (ZFPs) and are potent transcriptional repression modules. We have previously cloned a corepressor for the KRAB domain, KAP-1, which is required for KRAB-mediated repression in vivo. To characterize the repression mechanism utilized by KAP-1, we have analyzed the ability of KAP-1 to interact with murine (M31 and M32) and human (HP1α and HP1γ) homologues of the HP1 protein family, a class of nonhistone heterochromatin-associated proteins with a well-established epigenetic gene silencing function in Drosophila. In vitro studies confirmed that KAP-1 is capable of directly interacting with M31 and hHP1α, which are normally found in centromeric heterochromatin, as well as M32 and hHP1γ, both of which are found in euchromatin. Mapping of the region in KAP-1 required for HP1 interaction showed that amino acid substitutions which abolish HP1 binding in vitro reduce KAP-1 mediated repression in vivo. We observed colocalization of KAP-1 with M31 and M32 in interphase nuclei, lending support to the biochemical evidence that M31 and M32 directly interact with KAP-1. The colocalization of KAP-1 with M31 is sometimes found in subnuclear territories of potential pericentromeric heterochromatin, whereas colocalization of KAP-1 and M32 occurs in punctate euchromatic domains throughout the nucleus. This work suggests a mechanism for the recruitment of HP1-like gene products by the KRAB-ZFP–KAP-1 complex to specific loci within the genome through formation of heterochromatin-like complexes that silence gene activity. We speculate that gene-specific repression may be a consequence of the formation of such complexes, ultimately leading to silenced genes in newly formed heterochromatic chromosomal environments.

Abstract B5: Reversing epigenetic gene silencing to overcome immune evasion in CNS malignancies

2020 ◽  
Author(s):  
Nivedita M. Ratnam ◽  
Heather M. Sonnemann ◽  
Mark R. Gilbert ◽  
Amber J. Giles
Keyword(s):  
Gene Silencing ◽  
Immune Evasion ◽  
Epigenetic Gene Silencing ◽  
Cns Malignancies

scholarly journals Epigenetic Modulation of Self-Renewal Capacity of Leukemic Stem Cells and Implications for Chemotherapy

Epigenomes ◽  
2020 ◽  
Vol 4 (1) ◽  
pp. 3
Author(s):  
Richard Momparler ◽  
Sylvie Côté ◽  
Louise Momparler
Keyword(s):  
Stem Cells ◽  
Gene Silencing ◽  
Epigenetic Therapy ◽  
Proliferative Potential ◽  
Primary Role ◽  
Leukemic Stem Cells ◽  
Self Renewal ◽  
Epigenetic Gene Silencing ◽  
Idh Mutations

Most patients with acute myeloid leukemia (AML) have a poor prognosis. Curative therapy of AML requires the complete eradication of the leukemic stem cells (LSCs). One aspect of LSCs that is poorly understood is their low frequency in the total population of leukemic cells in AML patients. After each cell division of LSCs, most of the daughter cells lose their capacity for self-renewal. Investigations into the role of Isocitrate dehydrogenase (IDH) mutations in AML provide some insight on the regulation of the proliferation of LSCs. The primary role of IDH is to convert isocitrate to alpha-keto-glutarate (α-KG). When IDH is mutated, it converts α-KG to 2-hydroxyglutarate (2-HG), an inhibitor of the TET pathway and Jumonji-C histone demethylases (JHDMs). The demethylating action of these enzymes removes the epigenetic gene-silencing markers, DNA methylation, H3K27me3 and H3K9me2 and can lead to the differentiation of LSCs. This enzymatic action is blocked by 2-HG in mutated IDH (mut-IDH) AML patients, who can be induced into remission with antagonists of 2-HG. These observations suggest that there exists in cells a natural enzymatic mechanism that uses demethylation to reverse epigenetic gene-silencing, leading to a loss of the self-renewal capacity of LSCs. This mechanism limits the proliferative potential of LSCs. Epigenetic agents that inhibit DNA and histone methylation exhibit a synergistic antineoplastic action on AML cells. It is possible that the therapeutic potential of this epigenetic therapy may be enhanced by demethylation enzymes, resulting in a very effective treatment for AML.

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