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A novel bromodomain inhibitor reverses HIV-1 latency through specific binding with BRD4 to promote Tat and P-TEFb association.
Huang H, et al.
Frontiers in Microbiology, 8, 1035-1035 (2017)
Hongzhen Li et al.
Scientific reports, 10(1), 21924-21924 (2020-12-16)
Olfactomedin 4 (OLFM4) is expressed in normal prostate epithelial cells and immortalized normal human prostate epithelial cells (RWPE1), but the identity of OLFM4-expressing cells within these populations and OLFM4's physiological functions in these cells have not been elucidated. Using single-cell...
Epigenetic chemical probes.
Muller S and Brown PJ
Clinical Pharmacology and Therapeutics, 92(6), 689-693 (2012)
Olga Vladimirova et al.
PLoS pathogens, 17(1), e1009231-e1009231 (2021-01-21)
Liquid-liquid phase separation (LLPS) can drive formation of diverse and essential macromolecular structures, including those specified by viruses. Kaposi's Sarcoma-Associated Herpesvirus (KSHV) genomes associate with the viral encoded Latency-Associated Nuclear Antigen (LANA) to form stable nuclear bodies (NBs) during latent...
Shuhei Ishikura et al.
Nucleic acids research, 48(19), 10848-10866 (2020-10-01)
Centromeres are genomic regions essential for faithful chromosome segregation. Transcription of noncoding RNA (ncRNA) at centromeres is important for their formation and functions. Here, we report the molecular mechanism by which the transcriptional regulator ZFAT controls the centromeric ncRNA transcription...
Agnieszka Wojtczak
Cells, 9(6) (2020-06-04)
Bromodomain containing (BRD) proteins play an essential role in many cellular processes. The aim of this study was to estimate activity of bromodomains during alga Chara vulgaris spermatids differentiation. The effect of a bromodomain inhibitor, JQ1 (100 µM), on the...
Liang-Fu Chen et al.
Cell reports, 26(5), 1174-1188 (2019-01-31)
Neuronal activity-inducible gene transcription correlates with rapid and transient increases in histone acetylation at promoters and enhancers of activity-regulated genes. Exactly how histone acetylation modulates transcription of these genes has remained unknown. We used single-cell in situ transcriptional analysis to...
Briana C Prager et al.
Cancer discovery, 10(11), 1722-1741 (2020-07-25)
Meningiomas are the most common primary intracranial tumor with current classification offering limited therapeutic guidance. Here, we interrogated meningioma enhancer landscapes from 33 tumors to stratify patients based upon prognosis and identify novel meningioma-specific dependencies. Enhancers robustly stratified meningiomas into...
Yaping Wu et al.
Theranostics, 9(6), 1777-1793 (2019-05-01)
The bromodomain and extraterminal family members are epigenetic readers and transcriptional coactivators which are critically involved in various biological processes including tumorigenesis. BRD4 has been increasingly appreciated as a key oncogene and promising anticancer target. Here, we sought to characterize...
Weili Kong et al.
PLoS pathogens, 16(3), e1008430-e1008430 (2020-03-17)
Recent efforts have been paid to identify previously unrecognized HIV-1 latency-promoting genes (LPGs) that can potentially be targeted for eradication of HIV-1 latent reservoirs. From our earlier orthologous RNAi screens of host factors regulating HIV-1 replication, we identified that the...
Dylan J Richards et al.
Nature biomedical engineering, 4(4), 446-462 (2020-04-15)
Environmental factors are the largest contributors to cardiovascular disease. Here we show that cardiac organoids that incorporate an oxygen-diffusion gradient and that are stimulated with the neurotransmitter noradrenaline model the structure of the human heart after myocardial infarction (by mimicking...
Aileen Patricia Szczepanski et al.
Genome medicine, 12(1), 63-63 (2020-07-17)
Small cell lung cancer (SCLC) is a more aggressive subtype of lung cancer that often results in rapid tumor growth, early metastasis, and acquired therapeutic resistance. Consequently, such phenotypical characteristics of SCLC set limitations on viable procedural options, making it...
Seung Woo Cho et al.
Cell, 173(6), 1398-1412 (2018-05-08)
Noncoding mutations in cancer genomes are frequent but challenging to interpret. PVT1 encodes an oncogenic lncRNA, but recurrent translocations and deletions in human cancers suggest alternative mechanisms. Here, we show that the PVT1 promoter has a tumor-suppressor function that is independent...
Anurag Rathore et al.
Scientific reports, 10(1), 5350-5350 (2020-03-27)
The major barrier to a HIV-1 cure is the persistence of latent genomes despite treatment with antiretrovirals. To investigate host factors which promote HIV-1 latency, we conducted a genome-wide functional knockout screen using CRISPR-Cas9 in a HIV-1 latency cell line...
Melyssa S Roberts et al.
Cancer research, 80(8), 1693-1706 (2020-02-15)
A significant therapeutic challenge for patients with cancer is resistance to chemotherapies such as taxanes. Overexpression of LIN9, a transcriptional regulator of cell-cycle progression, occurs in 65% of patients with triple-negative breast cancer (TNBC), a disease commonly treated with these...
Hunter R Gibbons et al.
Scientific reports, 9(1), 10280-10280 (2019-07-18)
As a class, 'BET' inhibitors disrupt binding of bromodomain and extra-terminal motif (BET) proteins, BRD2, BRD3, BRD4 and BRDT, to acetylated histones preventing recruitment of RNA polymerase 2 to enhancers and promoters, especially super-enhancers, to inhibit gene transcription. As such...
Kidong Kang et al.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 34(3), 4369-4383 (2020-02-07)
In tumor necrosis factor (TNF) signaling, phosphorylation and activation of receptor interacting protein kinase 1 (RIPK1) by upstream kinases is an essential checkpoint in the suppression of TNF-induced cell death. Thus, discovery of pharmacological agents targeting RIPK1 may provide new...
The BET bromodomain inhibitor JQ1 activates HIV latency through antagonizing Brd4 inhibition of Tat-transactivation.
Li Z, et al.
Nucleic Acids Research, 41(1), 277-287 (2012)
Vanessa Dubois et al.
Molecular systems biology, 16(5), e9156-e9156 (2020-05-15)
Liver injury triggers adaptive remodeling of the hepatic transcriptome for repair/regeneration. We demonstrate that this involves particularly profound transcriptomic alterations where acute induction of genes involved in handling of endoplasmic reticulum stress (ERS) is accompanied by partial hepatic dedifferentiation. Importantly...