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RUNX3 methylation drives hypoxia-induced cell proliferation andantiapoptosis in early tumorigenesis.
Published: October, 2020

Abstract: Inactivation of tumor suppressor Runt-related transcription factor 3 (RUNX3) plays an important role during early tumorigenesis. However, posttranslational modifications (PTM)-based mechanism for the inactivation of RUNX3 under hypoxia is still no...
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Battle of the sex chromosomes: competition between X- and Y-chromosomeencoded proteins for partner interaction and chromatin occupancy drivesmulti-copy gene expression and evolution in muroid rodents.
Published: July, 2020

Abstract: Transmission distorters (TDs) are genetic elements that favor their own transmission to the detriments of others. Slx/Slxl1 (Sycp3-like-X-linked and Slx-like1) and Sly (Sycp3-like-Y-linked) are TDs which have been co-amplified on the X and Y chrom...
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Dysregulation of BRD4 Function Underlies the Functional Abnormalities of MeCP2 Mutant Neurons.
Published: June, 2020

Abstract: Rett syndrome (RTT), mainly caused by mutations in methyl-CpG binding protein 2 (MeCP2), is one of the most prevalent intellectual disorders without effective therapies. Here, we used 2D and 3D human brain cultures to investigate MeCP2 function. W...
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MYC transcription activation mediated by OCT4 as a mechanism of resistance to 13-cisRA-mediated differentiation in neuroblastoma.
Published: May, 2020

Abstract: Despite the improvement in clinical outcome with 13-cis-retinoic acid (13-cisRA) + anti-GD2 antibody + cytokine immunotherapy given in first response ~40% of high-risk neuroblastoma patients die of recurrent disease. MYCN genomic amplification is ...
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CRISPR off-target detection with DISCOVER-seq.
Published: April, 2020

Abstract: DISCOVER-seq (discovery of in situ Cas off-targets and verification by sequencing) is a broadly applicable approach for unbiased CRISPR-Cas off-target identification in cells and tissues. It leverages the recruitment of DNA repair factors to doubl...
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LncRNA np_5318 promotes renal ischemia‑reperfusion injury through the TGF‑β/Smad signaling pathway
Published: February, 2020

Abstract: Long noncoding (Lnc)RNA np_5318 has been proved to be involved in renal injury, while its functionality in renal ischemia‑reperfusion (I/R) injury is unknown. Therefore, the present study aimed to investigate the role of lncRNA np_5318 in the deve...
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Pro-death signaling of cytoprotective heat shock factor 1: upregulation of NOXA leading to apoptosis in heat-sensitive cells.
Published: January, 2020

Abstract: Heat shock can induce either cytoprotective mechanisms or cell death. We found that in certain human and mouse cells, including spermatocytes, activated heat shock factor 1 (HSF1) binds to sequences located in the intron(s) of the PMAIP1 (NOXA) ge...
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17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells.
Published: October, 2019

Abstract: Heat Shock Factor 1 (HSF1) is a key regulator of gene expression during acute environmental stress that enables the cell survival, which is also involved in different cancer-related processes. A high level of HSF1 in estrogen receptor (ER)-positiv...
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Cooperation of cancer drivers with regulatory germline variants shapes clinical outcomes.
Published: September, 2019

Abstract: Pediatric malignancies including Ewing sarcoma (EwS) feature a paucity of somatic alterations except for pathognomonic driver-mutations that cannot explain overt variations in clinical outcome. Here, we demonstrate in EwS how cooperation of domina...
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The Toxoplasma effector TEEGR promotes parasite persistence by modulating NF-κB signalling via EZH2.
Published: July, 2019

Abstract: The protozoan parasite Toxoplasma gondii has co-evolved with its homeothermic hosts (humans included) strategies that drive its quasi-asymptomatic persistence in hosts, hence optimizing the chance of transmission to new hosts. Persistence, which s...
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Preformed chromatin topology assists transcriptional robustness of during limb development.
Published: May, 2019

Abstract: Long-range gene regulation involves physical proximity between enhancers and promoters to generate precise patterns of gene expression in space and time. However, in some cases, proximity coincides with gene activation, whereas, in others, preform...
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NRG1 is a critical regulator of differentiation in TP63-driven squamous cell carcinoma.
Published: May, 2019

Abstract: Squamous cell carcinomas (SCCs) account for the majority of cancer mortalities. Although TP63 is an established lineage-survival oncogene in SCCs, therapeutic strategies have not been developed to target TP63 or it's downstream effectors. In this ...
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Guidelines for optimized gene knockout using CRISPR/Cas9
Published: May, 2019

Abstract: CRISPR/Cas9 technology has evolved as the most powerful approach to generate genetic models both for fundamental and preclinical research. Despite its apparent simplicity, the outcome of a genome-editing experiment can be substantially impacted by...
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Maintenance of MYC expression promotes de novo resistance to BET bromodomain inhibition in castration-resistant prostate cancer.
Published: March, 2019

Abstract: The BET bromodomain protein BRD4 is a chromatin reader that regulates transcription, including in cancer. In prostate cancer, specifically, the anti-tumor activity of BET bromodomain inhibition has been principally linked to suppression of androge...
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EZH2 is overexpressed in transitional preplasmablasts and is involved in human plasma cell differentiation.
Published: February, 2019

Abstract: Plasma cells (PCs) play a major role in the defense of the host organism against pathogens. We have shown that PC generation can be modeled using multi-step culture systems that reproduce the sequential cell differentiation occurring in vivo. Usin...
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Crosstalk Between Glucocorticoid Receptor and Early-growth Response Protein 1 Accounts for Repression of Brain-derived Neurotrophic Factor Transcript 4 Expression.
Published: February, 2019

Abstract: The brain-derived neurotrophic factor (BDNF) is a key player in brain functions such as synaptic plasticity, stress, and behavior. Its gene structure in rodents contains 8 untranslated exons (I to VIII) whose expression is finely regulated and whi...
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Epigenetic Co-Deregulation of EZH2/TET1 is a Senescence-Countering, Actionable Vulnerability in Triple-Negative Breast Cancer.
Published: January, 2019

Abstract: Triple-negative breast cancer (TNBC) cells lack the expression of ER, PR and HER2. Thus, TNBC patients cannot benefit from hormone receptor-targeted therapy as non-TNBC patients, but can only receive chemotherapy as the systemic treatment and have...
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Glucocorticoids stimulate hypothalamic dynorphin expression accounting for stress-induced impairment of GnRH secretion during preovulatory period.
Published: January, 2019

Abstract: Stress-induced reproductive dysfunction is frequently associated with increased glucocorticoid (GC) levels responsible for suppressed GnRH/LH secretion and impaired ovulation. Besides the major role of the hypothalamic kisspeptin system, other key...
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The long noncoding RNA and nuclear paraspeckles are up-regulated by the transcription factor HSF1 in the heat shock response.
Published: December, 2018

Abstract: The long noncoding RNA (lncRNA) (nuclear enriched abundant transcript 1) is the architectural component of nuclear paraspeckles, and it has recently gained considerable attention as it is abnormally expressed in pathological conditions such as can...
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Aryl Hydrocarbon Receptor Signaling Cell Intrinsically Inhibits Intestinal Group 2 Innate Lymphoid Cell Function.
Published: November, 2018

Abstract: Innate lymphoid cells (ILCs) are important for mucosal immunity. The intestine harbors all ILC subsets, but how these cells are balanced to achieve immune homeostasis and mount appropriate responses during infection remains elusive. Here, we show ...
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RRAD, IL4I1, CDKN1A, and SERPINE1 genes are potentially co-regulated by NF-κB and p53 transcription factors in cells exposed to high doses of ionizing radiation.
Published: November, 2018

Abstract: BACKGROUND: The cellular response to ionizing radiation involves activation of p53-dependent pathways and activation of the atypical NF-κB pathway. The crosstalk between these two transcriptional networks include (co)regulation of common gen...
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H3K4me2 and WDR5 enriched chromatin interacting long non-coding RNAs maintain transcriptionally competent chromatin at divergent transcriptional units.
Published: October, 2018

Abstract: Recently lncRNAs have been implicated in the sub-compartmentalization of eukaryotic genome via genomic targeting of chromatin remodelers. To explore the function of lncRNAs in the maintenance of active chromatin, we characterized lncRNAs from the ...
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The long non-coding RNA NEAT1 and nuclear paraspeckles are upregulated by the transcription factor HSF1 in the heat shock response.
Published: October, 2018

Abstract: The long non-coding RNA (lncRNA) NEAT1 is the architectural component of nuclear paraspeckles, and has recently gained considerable attention as it is abnormally expressed in pathological conditions such as cancer and neurodegenerative diseases.&n...
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The Alzheimer's disease-associated TREM2 gene is regulated by p53 tumor suppressor protein.
Published: August, 2018

Abstract: TREM2 mutations evoke neurodegenerative disorders, and recently genetic variants of this gene were correlated to increased risk of Alzheimer's disease. The signaling cascade originating from the TREM2 membrane receptor includes its binding partner...
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Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility.
Published: August, 2018

Abstract: Ewing sarcoma (EWS) is a pediatric cancer characterized by the EWSR1-FLI1 fusion. We performed a genome-wide association study of 733 EWS cases and 1346 unaffected individuals of European ancestry. Our study replicates previously reported suscepti...
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The BRG1/SOX9 axis is critical for acinar cell-derived pancreatic tumorigenesis.
Published: August, 2018

Abstract: Chromatin remodeler Brahma related gene 1 (BRG1) is silenced in approximately 10% of human pancreatic ductal adenocarcinomas (PDAs). We previously showed that BRG1 inhibits the formation of intraductal pancreatic mucinous neoplasm (IPMN) and that ...
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Methyl-CpG-binding protein 2 mediates antifibrotic effects in scleroderma fibroblasts.
Published: August, 2018

Abstract: OBJECTIVE: Emerging evidence supports a role for epigenetic regulation in the pathogenesis of scleroderma (SSc). We aimed to assess the role of methyl-CpG-binding protein 2 (MeCP2), a key epigenetic regulator, in fibroblast activation and fibrosis...
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Pro-inflammatory cytokine and high doses of ionizing radiation have similar effects on the expression of NF-kappaB-dependent genes.
Published: June, 2018

Abstract: The NF-κB transcription factors are activated via diverse molecular mechanisms in response to various types of stimuli. A plethora of functions associated with specific sets of target genes could be regulated differentially by this factor, a...
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Corticosteroid receptors adopt distinct cyclical transcriptional signatures
Published: May, 2018

Abstract: Mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) are two closely related hormone-activated transcription factors that regulate major pathophysiologic functions. High homology between these receptors accounts for the crossbindin...
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Corticosteroid receptors adopt distinct cyclical transcriptional signatures.
Published: May, 2018

Abstract: Mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) are two closely related hormone-activated transcription factors that regulate major pathophysiologic functions. High homology between these receptors accounts for the crossbindin...
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Bcl11b, a novel GATA3-interacting protein, suppresses Th1 while limiting Th2 cell differentiation.
Published: May, 2018

Abstract: GATA-binding protein 3 (GATA3) acts as the master transcription factor for type 2 T helper (Th2) cell differentiation and function. However, it is still elusive how GATA3 function is precisely regulated in Th2 cells. Here, we show that the transcr...
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