NF-Y (CBF) regulation in specific cell types and mouse models

Maity, Sankar N.

doi:10.1016/j.bbagrm.2016.10.014

Cited by 32 publications

(28 citation statements)

References 58 publications

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“…This leads to a relaxed conformation of chromatin that impacts gene expression pattern, facilitating survival of the parasite [81]. Transcription factor CBF/NF-Y has been shown to be regulated in different cell types when submitted to different types of stress, such as mechanical stress, ER stress, and DNA damage-related stress, among others [82]. Its presence in EVs derived from drug-resistant parasites would reflect general adaptation mechanisms against drug-generated stress.…”

Section: Discussionmentioning

confidence: 99%

Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites

et al. 2020

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Leishmaniasis constitutes the 9 th largest disease burden among all infectious diseases. Control of this disease is based on a short list of chemotherapeutic agents headed by pentavalent antimonials, followed by miltefosine and amphotericin B; drugs that are far from ideal due to host toxicity, elevated cost, limited access, and high rates of drug resistance. Knowing that the composition of extracellular vesicles (EVs) can vary according to the state of their parental cell, we hypothesized that EVs released by drug-resistant Leishmania infantum parasites could contain unique and differently enriched proteins depending on the drugresistance mechanisms involved in the survival of their parental cell line. To assess this possibility, we studied EV production, size, morphology, and protein content of three well-characterized drug-resistant L. infantum cell lines and a wild-type strain. Our results are the first to demonstrate that drug-resistance mechanisms can induce changes in the morphology, size, and distribution of L. infantum EVs. In addition, we identified L. infantum's core EV proteome. This proteome is highly conserved among strains, with the exception of a handful of proteins that are enriched differently depending on the drug responsible for induction of antimicrobial resistance. Furthermore, we obtained the first snapshot of proteins enriched in EVs released by antimony-, miltefosine-and amphotericin-resistant parasites. These include several virulence factors, transcription factors, as well as proteins encoded by drugresistance genes. This detailed study of L. infantum EVs sheds new light on the potential roles of EVs in Leishmania biology, particularly with respect to the parasite's survival in stressful conditions. This work outlines a crucial first step towards the discovery of EVbased profiles capable of predicting response to antileishmanial agents.

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Section: Discussionmentioning

confidence: 99%

Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites

et al. 2020

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“…Previously, a role of NF-YA in gastric cancer has not been defined. 42 , 43 , 44 NF-YA is a subunit of the NF-Y heterotrimer, which has been suggested to aid tumor development by binding to promoter or enhancer regions of related genes. Its impact on gastric cancer development has not been described.…”

Section: Discussionmentioning

confidence: 99%

Analysis of cyclin E co‐expression genes reveals nuclear transcription factor Y subunit alpha is an oncogene in gastric cancer

Bie

et al. 2019

Chronic Diseases and Translational Medicine

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Objective To explore genes potentially co-expressed with cyclin E in gastric cancer and discover possible targets for gastric cancer treatment. Methods The Cancer Genome Atlas (TCGA) stomach adenocarcinoma sequencing data were used to predict genes co-expressed with cyclin E. Co-expression genes predicted by cBioPortal online analysis with Pearson correlation coefficient ≥0.4 were analyzed by gene ontology (GO) enrichment annotation using the PANTHER online platform (Ver. 7). Interactions between proteins encoded by these genes were analyzed using the STRING online platform (Ver. 10.5) and Cytoscape software (Ver. 3.5.1). Genes displaying a high degree of connection were analyzed by transcription factor enrichment prediction using FunRich software (Ver. 3). The significant transcription factor and cyclin E expression levels and their impact on gastric cancer progression were analyzed by Western blotting and Kaplan–Meier survival curve analysis. Results After filtering the co-expression gene prediction results, 78 predicted genes that included 73 protein coding genes and 5 non-coding genes with Pearson correlation coefficient ≥0.4 were selected. The expressions of the genes were considered to be correlated with cyclin E expression. Among the 78 genes co-expressed with cyclin E, 19 genes at the central of the regulatory network associated with cyclin E were discovered. Nuclear transcription factor Y subunit alpha (NF-YA) was identified as a significant transcription factor associated with cyclin E co-expressing genes. Analysis of specimen donors’ clinical records revealed that high expression of NF-YA tended to be associated with increased cyclin E expression. The expression of both was associated with progression of gastric cancer. Western blotting results showed that compared with normal tissues, NF-YA and cyclin E were highly expressed in tumor tissues ( P < 0.001). Survival curve analysis clearly demonstrated relatively poor overall survival of gastric cancer patients with high cyclin E or high NF-YA expression level, compared to patients with low cyclin E or NF-YA expression ( P < 0.05). Conclusions NF-YA may promote gastric cancer progression by increasing the transcription of cyclin E and other cell cycle regulatory genes. NF-YA might be a potential therapeutically useful prognostic factor for gastric cancer.

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“…Consistent with increased NNFs at promoters, there were far more footprint sites genome-wide identified for TF motifs with positive HINT scores, than those with negative scores (Fig 5C), which is indicative of increased overall TF binding. Examples of motifs identified include those for NF-YB and SP1 (Fig 5D & S5C), which are known to physically interact and have roles in developmental differentiation [46][47][48][49][50][51] . Taken together, these results provide strong evidence that ANP32E loss causes expansion of H2A.Z at promoters, and this H2A.Z reorganization coincides with improved nucleosome positioning, and increased TF binding.…”

Section: Tf-footprinting Increases Adjacent To Better Positioned H2amentioning

confidence: 99%

Genome-wide Chromatin Accessibility is Restricted by ANP32E

Murphy

Meng

Makowski

et al. 2020

Preprint

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Genome-wide chromatin state underlies gene expression potential and cellular function. Epigenetic features and nucleosome positioning contribute to the accessibility of DNA, but widespread regulators of chromatin state are largely unknown. Our study investigates how control of genomic H2A.Z localization by ANP32E contributes to chromatin state in mouse fibroblasts. We define H2A.Z as a universal chromatin accessibility factor, and demonstrate that through antagonism of H2A.Z, ANP32E restricts genome-wide DNA access. In the absence of ANP32E, H2A.Z accumulates at promoters in a hierarchical manner. H2A.Z initially localizes downstream of the transcription start site, and if H2A.Z is already present downstream, additional H2A.Z accumulates upstream. This hierarchical H2A.Z accumulation coincides with improved nucleosome positioning, heightened transcription factor binding, and increased expression of neighboring genes. Thus, ANP32E dramatically influences genome-wide chromatin accessibility through refinement of H2A.Z patterns, providing a means to reprogram chromatin state and to hone gene expression levels.

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NF-Y (CBF) regulation in specific cell types and mouse models

Cited by 32 publications

References 58 publications

Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites

Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites

Analysis of cyclin E co‐expression genes reveals nuclear transcription factor Y subunit alpha is an oncogene in gastric cancer

Genome-wide Chromatin Accessibility is Restricted by ANP32E

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