ATP-Dependent Nucleosome Remodeling

2018 ◽  
pp. 13-13
Keyword(s):  
Nucleosome Remodeling

2049-P: The Chd4 Helicase of the Nucleosome Remodeling and Deacetylase Complex Modulates Pdx1 Target Gene Expression In Vitro

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 2049-P
Author(s):  
REBECCA K. DAVIDSON ◽  
NOLAN CASEY ◽  
JASON SPAETH
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Nucleosome Remodeling ◽  
Target Gene Expression

The Development of Epigenetics and Related Inhibitors for Targeted Drug Design in Cancer Therapy

2019 ◽  
Vol 18 (28) ◽  
pp. 2380-2394 ◽  
Author(s):  
Na Liu ◽  
Rongtong Zhao ◽  
Yue Ma ◽  
Dongyuan Wang ◽  
Chen Yan ◽  
...  
Keyword(s):  
Drug Design ◽  
Rapid Development ◽  
Epigenetic Changes ◽  
Disease Treatment ◽  
Nucleosome Remodeling ◽  
Epigenetic Modifiers ◽  
The Us ◽  
Targeted Drug ◽  
Heritable Change ◽  
Lymphoma Therapy

Epigenetics process is the heritable change in gene function that does not involve changes in the DNA sequence. Until now, several types of epigenetic mechanisms have been characterized, including DNA methylation, histone modification (acetylation, methylation, etc.), nucleosome remodeling, and noncoding RNAs. With the biological investigations of these modifiers, some of them are identified as promoters in the process of various diseases, such as cancer, cardiovascular disease and virus infection. Epigenetic changes may serve as potential “first hits” for tumorigenesis. Hence, targeting epigenetic modifiers is being considered as a promising way for disease treatment. To date, six agents in two epigenetic target classes (DNMT and HDAC) have been approved by the US Food and Drug Administration (FDA). Most of these drugs are applied in leukemia, lymphoma therapy, or are combined with other drugs for the treatment of solid tumor. Due to the rapid development of epigenetics and epigenetics targeted drugs, it is becoming an emerging area in targeted drug design.

scholarly journals Restoration of Silencing in Saccharomyces cerevisiae by Tethering of a Novel Sir2-Interacting Protein, Esc8

Genetics ◽  
2002 ◽  
Vol 162 (2) ◽  
pp. 633-645 ◽  
Author(s):  
Guido Cuperus ◽  
David Shore
Keyword(s):  
Protein A ◽  
Dominant Negative ◽  
Class I ◽  
Dominant Negative Effect ◽  
Rna Pol Ii ◽  
Interacting Protein ◽  
Nucleosome Remodeling ◽  
Negative Effect ◽  
Close Homolog

Abstract We previously described two classes of SIR2 mutations specifically defective in either telomeric/HM silencing (class I) or rDNA silencing (class II) in S. cerevisiae. Here we report the identification of genes whose protein products, when either overexpressed or directly tethered to the locus in question, can establish silencing in SIR2 class I mutants. Elevated dosage of SCS2, previously implicated as a regulator of both inositol biosynthesis and telomeric silencing, suppressed the dominant-negative effect of a SIR2-143 mutation. In a genetic screen for proteins that restore silencing when tethered to a telomere, we isolated ESC2 and an uncharacterized gene, (YOL017w), which we call ESC8. Both Esc2p and Esc8p interact with Sir2p in two-hybrid assays, and the Esc8p-Sir2 interaction is detected in vitro. Interestingly, Esc8p has a single close homolog in yeast, the ISW1-complex factor Ioc3p, and has also been copurified with Isw1p, raising the possibility that Esc8p is a component of an Isw1p-containing nucleosome remodeling complex. Whereas esc2 and esc8 deletion mutants alone have only marginal silencing defects, cells lacking Isw1p show a strong silencing defect at HMR but not at telomeres. Finally, we show that Esc8p interacts with the Gal11 protein, a component of the RNA pol II mediator complex.

ZBTB2 protein is a new partner of the Nucleosome Remodeling and Deacetylase (NuRD) complex

2021 ◽  
Vol 168 ◽  
pp. 67-76
Author(s):  
Rosita Russo ◽  
Veronica Russo ◽  
Francesco Cecere ◽  
Mariangela Valletta ◽  
Maria Teresa Gentile ◽  
...  
Keyword(s):  
Nurd Complex ◽  
Nucleosome Remodeling

scholarly journals A Phosphomimetic Mutation in the Sall1 Repression Motif Disrupts Recruitment of the Nucleosome Remodeling and Deacetylase Complex and Repression ofGbx2

2007 ◽  
Vol 282 (48) ◽  
pp. 34858-34868 ◽  
Author(s):  
Shannon M. Lauberth ◽  
Amy C. Bilyeu ◽  
Beth A. Firulli ◽  
Kristen L. Kroll ◽  
Michael Rauchman
Keyword(s):  
Nucleosome Remodeling

scholarly journals IMiDs prime myeloma cells for daratumumab-mediated cytotoxicity through loss of Ikaros and Aiolos

Blood ◽  
2018 ◽  
Vol 132 (20) ◽  
pp. 2166-2178 ◽  
Author(s):  
Pasquale L. Fedele ◽  
Simon N. Willis ◽  
Yang Liao ◽  
Michael S. Low ◽  
Jai Rautela ◽  
...  
Keyword(s):  
Cell Death ◽  
Regulatory Networks ◽  
Nk Cell ◽  
Surface Expression ◽  
Nucleosome Remodeling ◽  
Interferon Stimulated Genes ◽  
Cd38 Expression ◽  
Cycle Arrest ◽  
Transcriptional Changes ◽  
Insight Into

Abstract Recent studies have demonstrated that the immunomodulatory drugs (IMiDs) lead to the degradation of the transcription factors Ikaros and Aiolos. However, why their loss subsequently leads to multiple myeloma (MM) cell death remains unclear. Using CRISPR-Cas9 genome editing, we have deleted IKZF1/Ikaros and IKZF3/Aiolos in human MM cell lines to gain further insight into their downstream gene regulatory networks. Inactivation of either factor alone recapitulates the cell intrinsic action of the IMiDs, resulting in cell cycle arrest and induction of apoptosis. Furthermore, evaluation of the transcriptional changes resulting from their loss demonstrates striking overlap with lenalidomide treatment. This was not dependent on reduction of the IRF4-MYC “axis,” as neither protein was consistently downregulated, despite cell death occurring, and overexpression of either factor failed to rescue for Ikaros loss. Importantly, Ikaros and Aiolos repress the expression of interferon-stimulated genes (ISGs), including CD38, and their loss led to the activation of an interferon-like response, contributing to MM cell death. Ikaros/Aiolos repressed CD38 expression through interaction with the nucleosome remodeling and deacetylase complex in MM. IMiD-induced loss of Ikaros or treatment with interferon resulted in an upregulation of CD38 surface expression on MM cells, priming for daratumumab-induced NK cell-mediated antibody-dependent cellular cytotoxicity. These results give further insight into the mechanism of action of the IMiDs and provide mechanistic rationale for combination with anti-CD38 monoclonal antibodies.

The SWI/SNF and RSC Nucleosome Remodeling Complexes

2010 ◽  
pp. 2345-2356
Author(s):  
Nilanjana Chatterjee ◽  
Payel Sen ◽  
Blaine Bartholomew
Keyword(s):  
Nucleosome Remodeling

scholarly journals Dissection of acute stimulus-inducible nucleosome remodeling in mammalian cells

2019 ◽  
Author(s):  
Federico Comoglio ◽  
Marta Simonatto ◽  
Sara Polletti ◽  
Xin Liu ◽  
Stephen T. Smale ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Regulatory Elements ◽  
Micrococcal Nuclease ◽  
Nucleosome Remodeling ◽  
Nucleosome Dynamics ◽  
Nucleosome Organization ◽  
Regulatory Information ◽  
Different Types ◽  
Genomic Regions ◽  
The Impact

ABSTRACTAccessibility of the genomic regulatory information is largely controlled by the nucleosome-organizing activity of transcription factors (TFs). Whereas stimulus-induced TFs bind to genomic regions that are maintained accessible by lineage-determining TFs, they also increase accessibility of thousands of cis-regulatory elements. Nucleosome remodeling events underlying such changes and their interplay with basal positioning are unknown. Here, we devised a novel quantitative framework discriminating different types of nucleosome remodeling events in micrococcal nuclease ChIP-seq datasets and used it to analyze nucleosome dynamics at stimulus-regulated cis-regulatory elements. At enhancers, remodeling preferentially affected poorly positioned nucleosomes while sparing well-positioned nucleosomes flanking the enhancer core, indicating that inducible TFs do not suffice to overrule basal nucleosomal organization maintained by lineage-determining TFs. Remodeling events appeared to be combinatorially driven by multiple TFs, with distinct TFs showing however different remodeling efficiencies. Overall, these data provide a systematic view of the impact of stimulation on nucleosome organization and genome accessibility in mammalian cells.

scholarly journals A RUNX3 enhancer polymorphism associated with ankylosing spondylitis influences recruitment of Interferon Regulatory Factor 5 and factors of the Nucleosome Remodelling Deacetylase Complex in CD8+ T-cells

2019 ◽  
Author(s):  
Matteo Vecellio ◽  
Adrian Cortes ◽  
Sarah Bonham ◽  
Carlo Selmi ◽  
Julian C Knight ◽  
...  
Keyword(s):  
T Cells ◽  
Ankylosing Spondylitis ◽  
Cd8 T Cells ◽  
Binding Protein ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Nurd Complex ◽  
Nucleosome Remodeling ◽  
Nuclear Extracts ◽  
Functional Consequences

ABSTRACTObjectivesTo investigate the functional consequences of the single nucleotide polymorphism rs4648889 in a putative enhancer upstream of the RUNX3 promoter strongly associated with ankylosing spondylitis (AS).MethodsThe effects of rs4648889 on transcription factor (TF) binding were tested by DNA pull-down and quantitative mass spectrometry. The results were validated by electrophoretic mobility gel shift assays (EMSA), Western blot (WB) analysis of the pulled-down eluates, and chromatin immuno-precipitation (ChIP)-qPCR.ResultsSeveral TFs showed differential allelic binding to a 50bp DNA probe spanning rs4648889. Binding was increased to the AS-risk A allele for IKZF3 (aiolos) in nuclear extracts from CD8+ T-cells (3.7-fold, p<0.03) and several components of the NUcleosome Remodeling Deacetylase (NuRD) complex, including Chromodomain-Helicase-DNA-binding protein 4 (3.6-fold, p<0.05) and Retinoblastoma-Binding Protein 4 (4.1-fold, p<0.02). In contrast, binding of interferon regulatory factor (IRF) 5 was increased to the AS-protective G allele. These results were confirmed by EMSA, WB and ChIP-qPCR.ConclusionsThe association of AS with rs4648889 most likely results from its influence on the binding of this enhancer-like region to TFs, including IRF5, IKZF3 and members of the NuRD complex. Further investigation of these factors and RUNX3-related pathways may reveal important new therapeutic possibilities in AS.

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