Faculty Opinions recommendation of Noncoding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability.

Backgrounds: Epigenetic regulation such as DNA methylation plays a major role in chromatin organization and gene transcription. Additionally, histone modification is an epigenetic regulator of chromatin structure and influences chromatin organization and gene expression. The relationship between DNA methyltransferase (DNMTs) expression and promoter methylation of the tumor suppressor genes (TSGs) has been reported in various cancers. Previously, the effect of 5-aza-2'-deoxycytidine (5-AZA-CdR), trichostatin A (TSA), and valproic acid (VPA) was shown on various cancers. This study aimed to investigate the effect of 5'-fluoro-2'-deoxycytidine (FdCyd) and sodium butyrate on the genes of the intrinsic apoptotic pathway, p21, p53, cell viability, and apoptosis in human hepatocellular carcinoma SNU449, SNU475, and SNU368 cell lines. Materials and Methods: In this lab trial study, the SNU449, SNU475, and SNU368 cells were cultured and treated with 5'-fluoro-2'-deoxycytidine and sodium butyrate. To determine cell viability, cell apoptosis, and the relative gene expression level, MTT assay, flow cytometry assay, and qRT-PCR were done respectively. Results: 5'-fluoro-2'-deoxycytidine and sodium butyrate changed the expression level of the BAX, BAK, APAF1, Bcl-2, Bcl-xL, p21, and p53 gene (P<0.0001) by which induced cell apoptosis and inhibit cell growth in all three cell lines, SNU449, SNU475, and SNU368. Conclusion: Both compounds played their roles through the intrinsic apoptotic pathway to induce cell apoptosis.

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Regulatory elements can be essential for maintaining broad chromatin organization and cell viability

10.1101/2020.12.13.422554 ◽

2020 ◽

Author(s):

Ying Liu ◽

Bo Ding ◽

Lina Zheng ◽

Ping Xu ◽

Zhiheng Liu ◽

...

Keyword(s):

Cell Death ◽

Cell Viability ◽

Cell Survival ◽

Chromatin Structure ◽

Synergistic Effects ◽

Regulatory Elements ◽

Essential Genes ◽

Chromatin Organization ◽

Cellular Functions ◽

3D Chromatin Structure

Increasing evidence shows that promoters and enhancers could be related to 3D chromatin structure, thus affecting cellular functions. Except for functioning through the canonical chromatin loops formed by promoters and enhancers, their roles in maintaining broad chromatin organization have not been well studied. Here, we focused on the active promoters/enhancers (referred to as hotspots) predicted to form many 3D contacts with other active promoters/enhancers, and identified dozens of loci critical for cell survival. While the essentiality of hotspots is not resulted from their association with essential genes, deletion of an essential hotspot could lead to change of broad chromatin organization and expressions of distal genes. We demonstrated that multiple affected genes that are individually non-essential could have synergistic effects to cause cell death.

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Noncoding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability

Science Advances ◽

10.1126/sciadv.abi6020 ◽

2021 ◽

Vol 7 (45) ◽

Author(s):

Bo Ding ◽

Ying Liu ◽

Zhiheng Liu ◽

Lina Zheng ◽

Ping Xu ◽

...

Keyword(s):

Cell Viability ◽

Chromatin Organization

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Non-coding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability

10.1101/2020.12.13.422541 ◽

2020 ◽

Author(s):

Bo Ding ◽

Ying Liu ◽

Zhiheng Liu ◽

Lina Zheng ◽

Ping Xu ◽

...

Keyword(s):

Gene Expression ◽

Protein Binding ◽

Cell Viability ◽

Single Cell ◽

Functional Element ◽

Chromatin Organization ◽

Coding Regions ◽

Structural Importance ◽

Powerful Approach ◽

Disease Specific

ABSTRACTThe majority of the non-coding regions in the human genome do not harbor any annotated element and are even not marked with any epigenomic signal or protein binding. An understudied aspect of these regions is their possible roles in stabilizing the 3D chromatin organization. To illuminate their “structural importance”, we chose to start with the non-coding regions forming many 3D contacts (referred to as hubs) and identified dozens of hubs essential for cell viability. Hi-C and single cell transcriptomic analyses showed that their deletion could significantly alter chromatin organization and impact gene expression located distal in the genome. This study revealed the 3D structural importance of non-coding loci that are not associated with any functional element, providing a new mechanistic understanding of the disease-associated genetic variations (GVs). Furthermore, our analyses also suggested a powerful approach to develop “one-drug-multiple-targets” therapeutics targeting the disease-specific non-coding regions.

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Cytoprotective Effect of Tocotrienol-Rich Fraction and α-Tocopherol Vitamin E Isoforms Against Glutamate-Induced Cell Death in Neuronal Cells

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000201 ◽

2014 ◽

Vol 84 (3-4) ◽

pp. 0140-0151 ◽

Cited By ~ 11

Author(s):

Thilaga Rati Selvaraju ◽

Huzwah Khaza’ai ◽

Sharmili Vidyadaran ◽

Mohd Sokhini Abd Mutalib ◽

Vasudevan Ramachandran ◽

...

Keyword(s):

Vitamin E ◽

Cell Viability ◽

Neuronal Cells ◽

Positive Control ◽

Post Treatment ◽

Mitochondrial Activity ◽

Before And After ◽

Pre Treatment ◽

Tocotrienol Rich Fraction ◽

Major Mediator

Glutamate is the major mediator of excitatory signals in the mammalian central nervous system. Extreme amounts of glutamate in the extracellular spaces can lead to numerous neurodegenerative diseases. We aimed to clarify the potential of the following vitamin E isomers, tocotrienol-rich fraction (TRF) and α-tocopherol (α-TCP), as potent neuroprotective agents against glutamate-induced injury in neuronal SK-N-SH cells. Cells were treated before and after glutamate injury (pre- and post-treatment, respectively) with 100 - 300 ng/ml TRF/α-TCP. Exposure to 120 mM glutamate significantly reduced cell viability to 76 % and 79 % in the pre- and post-treatment studies, respectively; however, pre- and post-treatment with TRF/α-TCP attenuated the cytotoxic effect of glutamate. Compared to the positive control (glutamate-injured cells not treated with TRF/α-TCP), pre-treatment with 100, 200, and 300 ng/ml TRF significantly improved cell viability following glutamate injury to 95.2 %, 95.0 %, and 95.6 %, respectively (p < 0.05).The isomers not only conferred neuroprotection by enhancing mitochondrial activity and depleting free radical production, but also increased cell viability and recovery upon glutamate insult. Our results suggest that vitamin E has potent antioxidant potential for protecting against glutamate injury and recovering glutamate-injured neuronal cells. Our findings also indicate that both TRF and α-TCP could play key roles as anti-apoptotic agents with neuroprotective properties.

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