keyword
MENU ▼
Read by QxMD icon Read
search

Bromodomain

keyword
https://www.readbyqxmd.com/read/28733670/brd3-and-brd4-bet-bromodomain-proteins-differentially-regulate-skeletal-myogenesis
#1
Thomas C Roberts, Usue Etxaniz, Alessandra Dall'Agnese, Shwu-Yuan Wu, Cheng-Ming Chiang, Paul E Brennan, Matthew J A Wood, Pier Lorenzo Puri
Myogenic differentiation proceeds through a highly coordinated cascade of gene activation that necessitates epigenomic changes in chromatin structure. Using a screen of small molecule epigenetic probes we identified three compounds which inhibited myogenic differentiation in C2C12 myoblasts; (+)-JQ1, PFI-1, and Bromosporine. These molecules target Bromodomain and Extra Terminal domain (BET) proteins, which are epigenetic readers of acetylated histone lysine tail residues. BETi-mediated anti-myogenic effects were also observed in a model of MYOD1-mediated myogenic conversion of human fibroblasts, and in primary mouse and human myoblasts...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28731328/bisphosphonate-functionalized-hydroxyapatite-nanoparticles-for-the-delivery-of-the-bromodomain-inhibitor-jq1-in-the-treatment-of-osteosarcoma
#2
Victoria Wu, Jarrett Mickens, Vuk Uskokovic
Osteosarcoma (OS) is one of the most common neoplasia among children and its survival statistics have been stagnating since the combinatorial anticancer therapy triad was first introduced. Here we report on the assessment of the effect of hydroxyapatite (HAp) nanoparticles loaded with medronate, the simplest bisphosphonate, as a bone-targeting agent and JQ1, a small-molecule bromodomain inhibitor, as a chemotherapeutic in different 2D and 3D K7M2 OS in vitro models. Both additives decreased the crystallinity of HAp, but the effect was more intense for medronate because of its higher affinity for HAp...
July 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28726418/quantitative-assessment-of-the-effects-of-trypsin-digestion-methods-on-affinity-purification-mass-spectrometry-based-protein-protein-interaction-analysis
#3
Yueqing Zhang, Hong Sun, Jing Zhang, Allan R Brasier, Yingxin Zhao
Affinity purification-mass spectrometry (AP-MS) has become the method of choice for discovering protein-protein interactions (PPIs) under native conditions. The success of AP-MS depends on the efficiency of trypsin digestion and the recovery of the tryptic peptides for MS analysis. Several different protocols have been used for trypsin digestion of protein complexes in AP-MS studies, but no systematic studies have been conducted on the impact of trypsin digestion conditions on the identification of PPIs. Here, we used NFκB/RelA and Bromodomain-containing protein 4 (BRD4) as baits and test five distinct trypsin digestion methods (two using "on-beads," three using "elution-digestion" protocols)...
July 20, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28725161/ep300-single-nucleotide-polymorphism-rs20551-correlates-with-prolonged-overall-survival-in-diffuse-large-b-cell-lymphoma-patients-treated-with-r-chop
#4
Jiao Li, Ning Ding, Xiaogan Wang, Lan Mi, Lingyan Ping, Xuan Jin, Yalu Liu, Zhitao Ying, Yan Xie, Weiping Liu, Yuqin Song, Jun Zhu
BACKGROUND: Rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) is used as standard frontline regimen for diffuse large B-cell lymphoma (DLBCL). The landscape of somatic mutations in DLBCL revealed that inactivation of EP300 plays an important role in lymphomagenesis. A common EP300 single nucleotide polymorphism (SNP) rs20551 results in the substitution of valine for isoleucine at codon 997 close to the Bromodomain. However, the association between SNP rs20551 and clinical prognosis in DLBCL patients treated with R-CHOP is unknown...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28724615/glioblastoma-cellular-cross-talk-converges-on-nf-%C3%AE%C2%BAb-to-attenuate-egfr-inhibitor-sensitivity
#5
Ciro Zanca, Genaro R Villa, Jorge A Benitez, Amy Haseley Thorne, Tomoyuki Koga, Matteo D'Antonio, Shiro Ikegami, Jianhui Ma, Antonia D Boyer, Afsheen Banisadr, Nathan M Jameson, Alison D Parisian, Olesja V Eliseeva, Gabriela F Barnabe, Feng Liu, Sihan Wu, Huijun Yang, Jill Wykosky, Kelly A Frazer, Vladislav V Verkhusha, Maria G Isaguliants, William A Weiss, Timothy C Gahman, Andrew K Shiau, Clark C Chen, Paul S Mischel, Webster K Cavenee, Frank B Furnari
In glioblastoma (GBM), heterogeneous expression of amplified and mutated epidermal growth factor receptor (EGFR) presents a substantial challenge for the effective use of EGFR-directed therapeutics. Here we demonstrate that heterogeneous expression of the wild-type receptor and its constitutively active mutant form, EGFRvIII, limits sensitivity to these therapies through an interclonal communication mechanism mediated by interleukin-6 (IL-6) cytokine secreted from EGFRvIII-positive tumor cells. IL-6 activates a NF-κB signaling axis in a paracrine and autocrine manner, leading to bromodomain protein 4 (BRD4)-dependent expression of the prosurvival protein survivin (BIRC5) and attenuation of sensitivity to EGFR tyrosine kinase inhibitors (TKIs)...
July 19, 2017: Genes & Development
https://www.readbyqxmd.com/read/28723212/engineering-recombinant-protein-sensors-for-quantifying-histone-acetylation
#6
Oscar F Sanchez, Agnes Mendonca, Ana D Carneiro, Chongli Yuan
H3K14ac (acetylation of lysine 14 of histone H3) is one of the most important epigentic modifications. Aberrant changes in H3K14ac have been associated with various diseases, including cancers and neurological disorders. Tools that enable detection and quantification of H3K14ac levels in cell extracts and in situ are thus of critical importance to reveal its role in various biological processes. Current detection techniques of specific histone modifications, however, are constrained by tedious sample pretreatments, lack of quantitative accuracy, and reliance on high quality antibodies...
March 24, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28714904/brd9-inhibition-alone-or-in-combination-with-cytostatic-compounds-as-a-therapeutic-approach-in-rhabdoid-tumors
#7
Katja F Krämer, Natalia Moreno, Michael C Frühwald, Kornelius Kerl
Rhabdoid tumors (RT) are malignant neoplasms of early childhood. Despite intensive therapy, survival is poor and new treatment approaches are required. The only recurrent mutations in these tumors affect SMARCB1 and less commonly SMARCA4, both subunits of the chromatin remodeling complex SWItch/Sucrose Non-Fermentable (SWI/SNF). Loss of these two core subunits alters the function of the SWI/SNF complex, resulting in tumor development. We hypothesized that inhibition of aberrant SWI/SNF function by selective blockade of the BRD9 subunit of the SWI/SNF complex would reduce tumor cell proliferation...
July 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28714688/design-of-a-chemical-probe-for-the-bromodomain-and-plant-homeodomain-finger-containing-brpf-family-of-proteins
#8
Niall Igoe, Elliott D Bayle, Cynthia Tallant, Oleg Fedorov, Julia C Meier, Pavel Savitsky, Catherine Rogers, Yannick Morias, Sarah Scholze, Helen Boyd, Danen Cunoosamy, David M Andrews, Anne Cheasty, Paul E Brennan, Susanne Müller, Stefan Knapp, Paul V Fish
The bromodomain and PHD finger-containing (BRPF) family are scaffolding proteins important for the recruitment of histone acetyltransferases of the MYST family to chromatin. Here we describe NI-57 (16) as new pan-BRPF chemical probe of the bromodomain (BRD) of the BRPFs. Inhibitor 16 preferentially bound the BRD of BRPF1 and BRD1 over BRPF3, whereas binding to BRD9 was weaker. 16 has excellent selectivity over non-class IV BRD proteins. Target engagement of BRPF1B and BRD1 with 16 was demonstrated in nanoBRET and FRAP assays...
July 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28714212/fragment-based-drug-discovery-in-the-bromodomain-and-extra-terminal-domain-family
#9
REVIEW
Mostafa Radwan, Rabah Serya
Bromodomain and extra-terminal domain (BET) inhibition has emerged recently as a potential therapeutic target for the treatment of many human disorders such as atherosclerosis, inflammatory disorders, chronic obstructive pulmonary disease (COPD), some viral infections, and cancer. Since the discovery of the two potent inhibitors, I-BET762 and JQ1, different research groups have used different techniques to develop novel potent and selective inhibitors. In this review, we will be concerned with the trials that used fragment-based drug discovery (FBDD) approaches to discover or optimize BET inhibitors, also showing fragments that can be further optimized in future projects to reach novel potent BET inhibitors...
July 17, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28710461/bromodomain-factors-of-bet-family-are-new-essential-actors-of-pericentric-heterochromatin-transcriptional-activation-in-response-to-heat-shock
#10
Edwige Col, Neda Hoghoughi, Solenne Dufour, Jessica Penin, Sivan Koskas, Virginie Faure, Maria Ouzounova, Hector Hernandez-Vargash, Nicolas Reynoird, Sylvain Daujat, Eric Folco, Marc Vigneron, Robert Schneider, André Verdel, Saadi Khochbin, Zdenko Herceg, Cécile Caron, Claire Vourc'h
The heat shock response is characterized by the transcriptional activation of both hsp genes and noncoding and repeated satellite III DNA sequences located at pericentric heterochromatin. Both events are under the control of Heat Shock Factor I (HSF1). Here we show that under heat shock, HSF1 recruits major cellular acetyltransferases, GCN5, TIP60 and p300 to pericentric heterochromatin leading to a targeted hyperacetylation of pericentric chromatin. Redistribution of histone acetylation toward pericentric region in turn directs the recruitment of Bromodomain and Extra-Terminal (BET) proteins BRD2, BRD3, BRD4, which are required for satellite III transcription by RNAP II...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28706277/dna-binding-drives-the-association-of-brg1-hbrm-bromodomains-with-nucleosomes
#11
Emma A Morrison, Julio C Sanchez, Jehnna L Ronan, Daniel P Farrell, Katayoun Varzavand, Jenna K Johnson, Brian X Gu, Gerald R Crabtree, Catherine A Musselman
BRG1 and BRM, central components of the BAF (mSWI/SNF) chromatin remodelling complex, are critical in chromatin structure regulation. Here, we show that the human BRM (hBRM) bromodomain (BRD) has moderate specificity for H3K14ac. Surprisingly, we also find that both BRG1 and hBRM BRDs have DNA-binding activity. We demonstrate that the BRDs associate with DNA through a surface basic patch and that the BRD and an adjacent AT-hook make multivalent contacts with DNA, leading to robust affinity and moderate specificity for AT-rich elements...
July 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28696689/correction-to-bet-bromodomain-inhibitors-with-one-step-synthesis-discovered-from-virtual-screen
#12
Alex M Ayoub, Laura M L Hawk, Ryan J Herzig, Jiewei Jiang, Andrea J Wisniewski, Clifford T Gee, Peiliang Zhao, Jin-Yi Zhu, Norbert Berndt, Nana K Offei-Addo, Thomas G Scott, Jun Qi, James E Bradner, Timothy R Ward, Ernst Schönbrunn, Gunda I Georg, William C K Pomerantz
No abstract text is available yet for this article.
July 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28696179/insights-into-the-crystal-structure-of-brd2-bd2-phenanthridinone-complex-and-theoretical-studies-on-phenanthridinone-analogs
#13
Shruti Mathur, Prashant Deshmukh, Shailesh Tripathi, Palaniappan Marimuthu, Balasundaram Padmanbhan
BET (Bromodomain and Extra-terminal) family proteins recognize the acetylated histone code on chromatin and participate in downstream processes like DNA replication, modification, and repair. As part of epigenetic approaches, BRD2 and BRD4 were identified as putative targets, for the management of chronic diseases. We have recently reported the discovery of a new scaffold of the phenanthridinone based inhibitor (L10) of the second bromodomain of BRD2 (BRD2-BD2). Here, we present the crystal structure of the BRD2-BD2, refined to 1...
July 11, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28695816/research-advances-in-the-role-of-bromodomain-containing-protein-4-in-epithelial-mesenchymal-transition-in-asthma
#14
Yan Zheng, Jun Wang, Qiugen Li
Asthma is a chronic airway disease characterized by airway inflammation and airway remodeling. Chronic airway inflammation can be involved in airway remodeling in asthmatic patients by incuding epithelial-mesenchymal transition (EMT).Bromodomain-containing protein 4 (BRD4) is a key transcriptional regulator in mammals,and many evidences have shown that BRD4 plays a pivotal role in airway remodeling via nuclear factor-κB/RelA signaling pathway. This review summarizes the recent advances in the role of BRD4 in regulating EMT,with an attempt to elucidate the molecular mechanisms of asthma and inform the prevention and control of asthma...
June 20, 2017: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/28694331/transcriptional-elongation-control-of-the-hbv-cccdna-transcription-by-super-elongation-complex-sec-and-brd4
#15
Joel Celio Francisco, Qian Dai, Zhuojuan Luo, Yan Wang, Roxanne Hui-Heng Chong, Yee Joo Tan, Wei Xie, Guan-Huei Lee, Chengqi Lin
Chronic hepatitis B virus (HBV) infection can lead to liver cirrhosis and hepatocellular carcinoma. HBV reactivation during or after chemotherapy is a potentially fatal complication for cancer patients with chronic HBV infection. Transcription of HBV is a critical intermediate step of HBV life cycle. However, factors controlling the HBV transcription remain largely unknown. Here, we found that different P-TEFb complexes are involved in the transcription of the HBV viral genome. Both BRD4 and the Super Elongation Complex (SEC) bind to the HBV genome...
July 10, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28689146/chemical-modulators-for-epigenome-reader-domains-as-emerging-epigenetic-therapies-for-cancer-and-inflammation
#16
REVIEW
Nilesh Zaware, Ming-Ming Zhou
Site-specific lysine acetylation and methylation on histones are critical post-translational modifications (PTMs) that govern ordered gene transcription in chromatin. Mis-regulation of these histone PTM-mediated processes has been shown to be associated with human diseases. Since the 2010 landmark reports of small molecules (+)-JQ1 and I-BET762 that target the acetyl-lysine 'reader' Bromodomain and Extra Terminal domain (BET) proteins, there have been relentless efforts to develop epigenetic therapy with small molecules to modulate molecular interactions of epigenome reader domain proteins with PTMs...
July 6, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28684431/convergent-roles-of-atf3-and-csl-in-chromatin-control-of-cancer-associated-fibroblast-activation
#17
Dong Eun Kim, Maria-Giuseppina Procopio, Soumitra Ghosh, Seung-Hee Jo, Sandro Goruppi, Francesco Magliozzi, Pino Bordignon, Victor Neel, Paolo Angelino, G Paolo Dotto
Cancer-associated fibroblasts (CAFs) are important for tumor initiation and promotion. CSL, a transcriptional repressor and Notch mediator, suppresses CAF activation. Like CSL, ATF3, a stress-responsive transcriptional repressor, is down-modulated in skin cancer stromal cells, and Atf3 knockout mice develop aggressive chemically induced skin tumors with enhanced CAF activation. Even at low basal levels, ATF3 converges with CSL in global chromatin control, binding to few genomic sites at a large distance from target genes...
July 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28680062/linking-functions-an-additional-role-for-an-intrinsically-disordered-linker-domain-in-the-transcriptional-coactivator-cbp
#18
Sara Contreras-Martos, Alessandro Piai, Simone Kosol, Mihaly Varadi, Angela Bekesi, Pierre Lebrun, Alexander N Volkov, Kris Gevaert, Roberta Pierattelli, Isabella C Felli, Peter Tompa
The multi-domain transcriptional coactivators CBP/p300 integrate a multitude of signaling inputs, interacting with more than 400 proteins via one or more of their globular domains. While CBP/p300 function is typically considered in terms of these structured domains, about half of the protein consists of intrinsically disordered regions (IDRs) of varying length. However, these IDRs have only been thought of as linkers that allow flexible spatial arrangement of the structured domains, but recent studies have shown that similar IDRs mediate specific and critical interactions in other proteins...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673542/bet-bromodomain-proteins-function-as-master-transcription-elongation-factors-independent-of-cdk9-recruitment
#19
Georg E Winter, Andreas Mayer, Dennis L Buckley, Michael A Erb, Justine E Roderick, Sarah Vittori, Jaime M Reyes, Julia di Iulio, Amanda Souza, Christopher J Ott, Justin M Roberts, Rhamy Zeid, Thomas G Scott, Joshiawa Paulk, Kate Lachance, Calla M Olson, Shiva Dastjerdi, Sophie Bauer, Charles Y Lin, Nathanael S Gray, Michelle A Kelliher, L Stirling Churchman, James E Bradner
Processive elongation of RNA Polymerase II from a proximal promoter paused state is a rate-limiting event in human gene control. A small number of regulatory factors influence transcription elongation on a global scale. Prior research using small-molecule BET bromodomain inhibitors, such as JQ1, linked BRD4 to context-specific elongation at a limited number of genes associated with massive enhancer regions. Here, the mechanistic characterization of an optimized chemical degrader of BET bromodomain proteins, dBET6, led to the unexpected identification of BET proteins as master regulators of global transcription elongation...
June 23, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28666361/identification-of-multiple-roles-for-histone-acetyltransferase-1-in-replication-coupled-chromatin-assembly
#20
Paula A Agudelo Garcia, Michael E Hoover, Pei Zhang, Prabakaran Nagarajan, Michael A Freitas, Mark R Parthun
Histone acetyltransferase 1 (Hat1) catalyzes the acetylation of newly synthesized histone H4 at lysines 5 and 12 that accompanies replication-coupled chromatin assembly. The acetylation of newly synthesized H4 occurs in the cytoplasm and the function of this acetylation is typically ascribed to roles in either histone nuclear import or deposition. Using cell lines from Hat1+/+ and Hat1-/- mouse embryos, we demonstrate that Hat1 is not required for either histone nuclear import or deposition. We employed quantitative proteomics to characterize Hat1-dependent changes in the composition of nascent chromatin structure...
June 28, 2017: Nucleic Acids Research
keyword
keyword
12451
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"