scholarly journals Disruption of TFIIH activities generates a stress gene expression response and reveals possible new targets against cancer

2019 ◽  
Author(s):  
Maritere Urioistegui-Arcos ◽  
Rodrigo Aguayo-Ortiz ◽  
María del Pilar Valencia-Morales ◽  
Erika Melchy-Pérez ◽  
Yvonne Rosenstein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumour Growth ◽  
Transformed Cells ◽  
Rna Seq ◽  
Gene Expression Response ◽  
New Targets ◽  
Increased Sensitivity ◽  
Promoter Occupancy ◽  
Expression Response ◽  
Stress Gene

AbstractDisruption of the enzymatic activities of the transcription factor TFIIH by Triptolide (TPL) or THZ1 could be used against cancer. Here, we used an oncogenesis model to compare the effect of TFIIH inhibitors between transformed cells and their progenitors. We report that tumour cells exhibited highly increased sensitivity to TPL or THZ1 and that the combination of both had an additive effect. TPL affects the interaction between XPB and P52, causing a reduction in the levels of XPB, P52, and P8, but not other TFIIH subunits. RNA-Seq and RNAPII-ChIP-Seq experiments showed that although the levels of many transcripts were reduced, the levels of a significant number were increased after TPL treatment, with maintained or increased RNAPII promoter occupancy. A significant number of these genes encode for factors that have been related to tumour growth and metastasis. Some of these genes were also overexpressed in response to THZ1, which depletion enhances the toxicity of TPL and are possible new targets against cancer.

scholarly journals Disruption of TFIIH activities generates a stress gene expression response and reveals possible new targets against cancer

Open Biology ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 200050 ◽  
Author(s):  
Maritere Uriostegui-Arcos ◽  
Rodrigo Aguayo-Ortiz ◽  
María del Pilar Valencia-Morales ◽  
Erika Melchy-Pérez ◽  
Yvonne Rosenstein ◽  
...  
Keyword(s):  
Small Molecules ◽  
Tumour Growth ◽  
Transformed Cells ◽  
Rna Seq ◽  
Gene Expression Response ◽  
New Targets ◽  
Increased Sensitivity ◽  
Promoter Occupancy ◽  
Expression Response ◽  
Stress Gene

Disruption of the enzymatic activities of the transcription factor TFIIH by the small molecules Triptolide (TPL) or THZ1 could be used against cancer. Here, we used the MCF10A-ErSrc oncogenesis model to compare the effect of TFIIH inhibitors between transformed cells and their progenitors. We report that tumour cells exhibited highly increased sensitivity to TPL or THZ1 and that the combination of both had a synergic effect. TPL affects the interaction between XPB and p52, causing a reduction in the levels of XPB, p52 and p8, but not other TFIIH subunits. RNA-Seq and RNAPII-ChIP-Seq experiments showed that although the levels of many transcripts were reduced, the levels of a significant number were increased after TPL treatment, with maintained or increased RNAPII promoter occupancy. A significant number of these genes encode for factors that have been related to tumour growth and metastasis, suggesting that transformed cells might rapidly develop resistance to TPL/THZ inhibitors. Some of these genes were also overexpressed in response to THZ1, of which depletion enhances the toxicity of TPL, and are possible new targets against cancer.

Author response for "Disruption of TFIIH activities generates a stress gene expression response and reveals possible new targets against cancer"

2020 ◽  
Author(s):  
Maritere Uriostegui-Arcos ◽  
Rodrigo Aguayo-Ortiz ◽  
María del Pilar Valencia-Morales ◽  
Erika Melchy-Pérez ◽  
Yvonne Rosenstein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Author Response ◽  
Gene Expression Response ◽  
New Targets ◽  
Expression Response ◽  
Stress Gene

scholarly journals Chromatin Dynamics and Gene Expression Response to Heat Exposure in Field-Conditioned versus Laboratory-Cultured Nematostella vectensis

2021 ◽  
Vol 22 (14) ◽  
pp. 7454
Author(s):  
Eviatar Weizman ◽  
Mieka Rinsky ◽  
Noa Simon-Blecher ◽  
Sarit Lampert-Karako ◽  
Orly Yaron ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acid Metabolism ◽  
Heat Exposure ◽  
Chromatin Accessibility ◽  
Nematostella Vectensis ◽  
Rna Seq ◽  
Short Term ◽  
Gene Expression Response ◽  
Chromatin Dynamics ◽  
Expression Response

Organisms’ survival is associated with the ability to respond to natural or anthropogenic environmental stressors. Frequently, these responses involve changes in gene regulation and expression, consequently altering physiology, development, or behavior. Here, we present modifications in response to heat exposure that mimics extreme summertime field conditions of lab-cultured and field-conditioned Nematostella vectensis. Using ATAC-seq and RNA-seq data, we found that field-conditioned animals had a more concentrated reaction to short-term thermal stress, expressed as enrichment of the DNA repair mechanism pathway. By contrast, lab animals had a more diffuse reaction that involved a larger number of differentially expressed genes and enriched pathways, including amino acid metabolism. Our results demonstrate that pre-conditioning affects the ability to respond efficiently to heat exposure in terms of both chromatin accessibility and gene expression and reinforces the importance of experimentally addressing ecological questions in the field.

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