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https://www.readbyqxmd.com/read/28334776/structural-characterization-of-interactions-between-transactivation-domain-1-of-the-p65-subunit-of-nf-%C3%AE%C2%BAb-and-transcription-regulatory-factors
#1
Lauriane Lecoq, Luca Raiola, Philippe R Chabot, Normand Cyr, Geneviève Arseneault, Pascale Legault, James G Omichinski
p65 is a member of the NF-κB family of transcriptional regulatory proteins that functions as the activating component of the p65-p50 heterodimer. Through its acidic transactivation domain (TAD), p65 has the capacity to form interactions with several different transcriptional regulatory proteins, including TFIIB, TFIIH, CREB-binding protein (CBP)/p300 and TAFII31. Like other acidic TADs, the p65 TAD contains two subdomains (p65TA1 and p65TA2) that interact with different regulatory factors depending on the target gene...
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28329675/trimethylation-and-acetylation-of-%C3%AE-catenin-at-lysine-49-represent-key-elements-in-esc-pluripotency
#2
Katrin Hoffmeyer, Dirk Junghans, Benoit Kanzler, Rolf Kemler
Wnt/β-catenin signaling is required for embryonic stem cell (ESC) pluripotency by inducing mesodermal differentiation and inhibiting neuronal differentiation; however, how β-catenin counter-regulates these differentiation pathways is unknown. Here, we show that lysine 49 (K49) of β-catenin is trimethylated (β-catMe3) by Ezh2 or acetylated (β-catAc) by Cbp. Significantly, β-catMe3 acts as a transcriptional co-repressor of the neuronal differentiation genes sox1 and sox3, whereas β-catAc acts as a transcriptional co-activator of the key mesodermal differentiation gene t-brachyury (t-bra)...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28322791/lps-depletes-phlpp-levels-in-macrophages-through-the-inhibition-of-sp1-dependent-transcriptional-regulation
#3
Neeraja P Alamuru-Yellapragada, Sanghamitra Vundyala, Soma Behera, Kishore V L Parsa
We have previously reported that bacterial endotoxin LPS attenuates expression of PHLPP, a ser/thr phosphatase, at both transcript and protein levels in different immune cells, however the underlying molecular mechanism is unknown and is of significant interest. Here, in line with the decreased transcript levels upon LPS treatment, we observed that LPS caused significant reduction in PHLPP promoter activity. We observed that SP1, a transcription factor frequently associated with inflammation, was recruited to the PHLPP promoter region...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28314773/glucocorticoid-receptor-signaling-represses-the-antioxidant-response-by-inhibiting-histone-acetylation-mediated-by-the-transcriptional-activator-nrf2
#4
Md Morshedul Alam, Keito Okazaki, Linh Thi Thao Nguyen, Nao Ota, Hiroshi Kitamura, Shohei Murakami, Hiroki Shima, Kazuhiko Igarashi, Hiroki Sekine, Hozumi Motohashi
NRF2 (nuclear factor erythroid 2-related factor 2) is a key transcriptional activator that mediates the inducible expression of antioxidant genes. NRF2 is normally ubiquitinated by KEAP1 (Kelch-like ECH-associated protein 1) and subsequently degraded by proteasomes. Inactivation of KEAP1 by oxidative stress or electrophilic chemicals allows NRF2 to activate transcription through binding to antioxidant response elements (AREs) and recruiting histone acetyltransferase CBP (CREB-binding protein). While KEAP1-dependent regulation is a major determinant of NRF2 activity, NRF2-mediated transcriptional activation varies from context to context, suggesting other intracellular signaling cascades may impact NRF2 function...
March 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28301306/two-possible-modes-of-pioneering-associated-with-combinations-of-h2a-z-and-p300-cbp-at-nucleosome-occupied-enhancers
#5
Pierre Cauchy, Frederic Koch, Jean-Christophe Andrau
Pioneer transcription factors are defined by their ability to bind nucleosome-occupied regions. Here, we discuss the properties of nucleosomes bound by pioneers at enhancer regions. We describe how select pioneers bind nucleosome-occupied or -depleted enhancer sites. Importantly, by revisiting and expanding existing data sets, we show differential H2A.Z and p300/CBP association at bound enhancers, highlighting two possible pioneering modes.
February 13, 2017: Transcription
https://www.readbyqxmd.com/read/28286521/pulling-a-ligase-out-of-a-hat-pcaf-mediates-ubiquitination-of-the-class-ii-transactivator
#6
Julie E Morgan, Susanna F Greer
The Class II Transactivator (CIITA) is essential to the regulation of Major Histocompatibility Class II (MHC II) genes transcription. As the "master regulator" of MHC II transcription, CIITA regulation is imperative and requires various posttranslational modifications (PTMs) in order to facilitate its role. Previously we identified various ubiquitination events on CIITA. Monoubiquitination is important for CIITA transactivity, while K63 linked ubiquitination is involved in crosstalk with ERK1/2 phosphorylation, where together they mediate cellular movement from the cytoplasm to nuclear region...
2017: International Journal of Cell Biology
https://www.readbyqxmd.com/read/28276606/smarca5-snf2h-is-required-for-proliferation-of-hematopoietic-stem-cells-differentiating-into-erythroid-and-myeloid-lineages
#7
Juraj Kokavec, Tomas Zikmund, Filipp Savvulidi, Vojtech Kulvait, Winfried Edelmann, Arthur I Skoultchi, Tomas Stopka
The Imitation Switch (ISWI) nuclear ATPase Smarca5 (Snf2h) is one of the most conserved chromatin remodeling factors. It exists in a variety of oligosubunit complexes that move DNA with respect to the histone octamer to generate regularly spaced nucleosomal arrays. Smarca5 interacts with different accessory proteins and represents a molecular motor for DNA replication, repair and transcription. We deleted Smarca5 at the onset of definitive hematopoiesis (Vav1-iCre) and observed that animals die during late fetal development due to anemia...
March 9, 2017: Stem Cells
https://www.readbyqxmd.com/read/28273070/hypersensitive-termination-of-the-hypoxic-response-by-a-disordered-protein-switch
#8
Rebecca B Berlow, H Jane Dyson, Peter E Wright
The cellular response to hypoxia is critical for cell survival and is fine-tuned to allow cells to recover from hypoxic stress and adapt to heterogeneous or fluctuating oxygen levels. The hypoxic response is mediated by the α-subunit of the transcription factor HIF-1 (HIF-1α), which interacts through its intrinsically disordered C-terminal transactivation domain with the TAZ1 (also known as CH1) domain of the general transcriptional coactivators CBP and p300 to control the transcription of critical adaptive genes...
March 16, 2017: Nature
https://www.readbyqxmd.com/read/28247282/backbone-1-h-13-c-and-15-n-nmr-resonance-assignments-of-the-kr%C3%A3-ppel-like-factor-4-activation-domain
#9
Brigid S Conroy, Emma R Weiss, Steven P Smith, David N Langelaan
Krüppel-like factor 4 (KLF4) is a transcription factor involved in diverse biological processes, including development, cellular differentiation and proliferation, and maintenance of tissue homeostasis. KLF4 has also been associated with disease states, such as cardiovascular disease and several cancers. KLF4 contains an activation domain, repression domain, and a structurally characterized C-terminal zinc finger domain that mediates its binding to DNA. The structurally uncharacterized KLF4 activation domain is critical for transactivation by KLF4 and mediates its binding to the transcriptional coactivator CBP/p300...
February 28, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28153533/dysregulation-of-gene-expression-in-the-striatum-of-bachd-rats-expressing-full-length-mutant-huntingtin-and-associated-abnormalities-on-molecular-and-protein-levels
#10
Libo Yu-Taeger, Michael Bonin, Janice Stricker-Shaver, Olaf Riess, Hoa Huu Phuc Nguyen
Huntington disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for the huntingtin protein (HTT). Mutant HTT (mHTT) has been proposed to cause neuronal dysfunction and neuronal loss through multiple mechanisms. Transcriptional changes may be a core pathogenic feature of HD. Utilizing the Affymetrix platform we performed a genome-wide RNA expression analysis in two BACHD transgenic rat lines (TG5 and TG9) at 12 months of age, both of which carry full-length human mHTT but with different expression levels...
January 30, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28128295/rna-helicase-ddx3-maintains-lipid-homeostasis-through-upregulation-of-the-microsomal-triglyceride-transfer-protein-by-interacting-with-hnf4-and-shp
#11
Tsung-Yuan Tsai, Wei-Ting Wang, Hao-Kang Li, Wei-Ju Chen, Yu-Hong Tsai, Chi-Hong Chao, Yan-Hwa Wu Lee
Multifunctional RNA helicase DDX3 participates in HCV infection, one of the major causes of hepatic steatosis. Here, we investigated the role of DDX3 in hepatic lipid metabolism. We found that HCV infection severely reduced DDX3 expression. Analysis of intracellular triglyceride and secreted ApoB indicated that lipid accumulations were increased while ApoB secretion were decreased in DDX3 knockdown HuH7 and HepG2 cell lines. Down-regulation of DDX3 significantly decreased protein and transcript expression of microsomal triglyceride transfer protein (MTP), a key regulator of liver lipid homeostasis...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28108460/enhancer-remodeling-during-adaptive-bypass-to-mek-inhibition-is-attenuated-by-pharmacologic-targeting-of-the-p-tefb-complex
#12
Jon S Zawistowski, Samantha M Bevill, Daniel R Goulet, Timothy J Stuhlmiller, Adriana S Beltran, Jose F Olivares-Quintero, Darshan Singh, Noah Sciaky, Joel S Parker, Naim U Rashid, Xin Chen, James S Duncan, Martin C Whittle, Steven P Angus, Sara Hanna Velarde, Brian T Golitz, Xiaping He, Charlene Santos, David B Darr, Kristalyn Gallagher, Lee M Graves, Charles M Perou, Lisa A Carey, H Shelton Earp, Gary L Johnson
Targeting the dysregulated BRAF-MEK-ERK pathway in cancer has increasingly emerged in clinical trial design. Despite clinical responses in specific cancers using inhibitors targeting BRAF and MEK, resistance develops often involving nongenomic adaptive bypass mechanisms. Inhibition of MEK1/2 by trametinib in patients with triple-negative breast cancer (TNBC) induced dramatic transcriptional responses, including upregulation of receptor tyrosine kinases (RTK) comparing tumor samples before and after one week of treatment...
March 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28077620/mitogen-induced-distinct-epi-alleles-are-phosphorylated-at-either-h3s10-or-h3s28-depending-on-h3k27-acetylation
#13
Dilshad H Khan, Shannon Healy, Shihua He, Daniel Lichtensztejn, Ludger Klewes, Kiran L Sharma, Veronica Lau, Sabine Mai, Geneviève P Delcuve, James R Davie
Stimulation of the MAPK pathway results in mitogen- and stress-activated protein kinase 1/2 (MSK1/2)-catalyzed phosphorylation of histone H3 at serine 10 or 28 and expression of immediate-early (IE) genes. In 10T1/2 mouse fibroblasts, phosphorylation of H3S10 and H3S28 occurs on different H3 molecules and in different nuclear regions. Likewise, we show that mitogen-induced H3S10 and H3S28 phosphorylation occurs in separate pools in human primary fibroblasts. High-resolution imaging studies on both cell types have revealed that H3S10 and H3S28 phosphorylation events can be induced in a single cell but on different alleles, giving rise to H3S10ph and H3S28ph epi-alleles...
January 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28076781/crtc1-nuclear-translocation-following-learning-modulates-memory-strength-via-exchange-of-chromatin-remodeling-complexes-on-the-fgf1-gene
#14
Shusaku Uchida, Brett J W Teubner, Charles Hevi, Kumiko Hara, Ayumi Kobayashi, Rutu M Dave, Tatsushi Shintaku, Pattaporn Jaikhan, Hirotaka Yamagata, Takayoshi Suzuki, Yoshifumi Watanabe, Stanislav S Zakharenko, Gleb P Shumyatsky
Memory is formed by synapse-to-nucleus communication that leads to regulation of gene transcription, but the identity and organizational logic of signaling pathways involved in this communication remain unclear. Here we find that the transcription cofactor CRTC1 is a critical determinant of sustained gene transcription and memory strength in the hippocampus. Following associative learning, synaptically localized CRTC1 is translocated to the nucleus and regulates Fgf1b transcription in an activity-dependent manner...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28069943/acetylation-promotes-tyrrs-nuclear-translocation-to-prevent-oxidative-damage
#15
Xuanye Cao, Chaoqun Li, Siyu Xiao, Yunlan Tang, Jing Huang, Shuan Zhao, Xueyu Li, Jixi Li, Ruilin Zhang, Wei Yu
Tyrosyl-tRNA synthetase (TyrRS) is well known for its essential aminoacylation function in protein synthesis. Recently, TyrRS has been shown to translocate to the nucleus and protect against DNA damage due to oxidative stress. However, the mechanism of TyrRS nuclear localization has not yet been determined. Herein, we report that TyrRS becomes highly acetylated in response to oxidative stress, which promotes nuclear translocation. Moreover, p300/CBP-associated factor (PCAF), an acetyltransferase, and sirtuin 1 (SIRT1), a NAD(+)-dependent deacetylase, regulate the nuclear localization of TyrRS in an acetylation-dependent manner...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28042453/design-and-synthesis-of-selective-small-molecule-inhibitors-of-coactivator-associated-arginine-methyltransferase-1-carm1
#16
H Ü Kaniskan, M S Eram, J Liu, D Smil, M L Martini, Y Shen, V Santhakumar, P J Brown, C Arrowsmith, M Vedadi, J Jin
Coactivator-associated arginine methyltransferase 1 (CARM1) is a type I protein arginine methyltransferase (PRMT) that catalyzes the conversion of arginine into monomethylarginine (MMA) and further into asymmetric dimethylarginine (ADMA). CARM1 methylates histone 3 arginines 17 and 26, as well as numerous non-histone proteins including CBP/p300, SRC-3, NCOA2, PABP1, and SAP49, while also functioning as a coactivator for various proteins that have been linked to cancer such as p53, NF-κβ, β-catenin, E2F1 and steroid hormone receptor ERα...
September 1, 2016: MedChemComm
https://www.readbyqxmd.com/read/27934915/the-defining-dna-methylation-signature-of-floating-harbor-syndrome
#17
Rebecca L Hood, Laila C Schenkel, Sarah M Nikkel, Peter J Ainsworth, Guillaume Pare, Kym M Boycott, Dennis E Bulman, Bekim Sadikovic
Floating-Harbor syndrome (FHS) is an autosomal dominant genetic condition characterized by short stature, delayed osseous maturation, expressive language impairment, and unique facial dysmorphology. We previously identified mutations in the chromatin remodeling protein SRCAP (SNF2-related CBP Activator Protein) as the cause of FHS. SRCAP has multiple roles in chromatin and transcriptional regulation; however, specific epigenetic consequences of SRCAP mutations remain to be described. Using high resolution genome-wide DNA methylation analysis, we identified a unique and highly specific DNA methylation "epi-signature" in the peripheral blood of individuals with FHS...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27933067/peptide-idr-1002-inhibits-nf-%C3%AE%C2%BAb-nuclear-translocation-by-inhibition-of-i%C3%AE%C2%BAb%C3%AE-degradation-and-activates-p38-erk1-2-msk1-dependent-creb-phosphorylation-in-macrophages-stimulated-with-lipopolysaccharide
#18
Alejandro Huante-Mendoza, Octavio Silva-García, Javier Oviedo-Boyso, Robert E W Hancock, Víctor M Baizabal-Aguirre
The inflammatory response is a critical molecular defense mechanism of the innate immune system that mediates the elimination of disease-causing bacteria. Repair of the damaged tissue, and the reestablishment of homeostasis, must be accomplished after elimination of the pathogen. The innate defense regulators (IDRs) are short cationic peptides that mimic natural host defense peptides and are effective in eliminating pathogens by enhancing the activity of the immune system while controlling the inflammatory response...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27926504/the-immunomodulatory-effects-of-tnf-%C3%AE-inhibitors-on-human-th17-cells-via-ror%C3%AE-t-histone-acetylation
#19
Yi-Ching Lin, Yu-Chih Lin, Cheng-Chin Wu, Ming-Yii Huang, Wen-Chan Tsai, Chih-Hsing Hung, Po-Lin Kuo
The presence of interleukin (IL)-17-related cytokines correlates with rheumatoid arthritis (RA) pathogenesis. Epigenetic modifications, including histone acetylation, regulate gene expression in RA pathogenesis. Tumour necrosis factor-alpha (TNF-α) inhibitors such as etanercept and adalimumab, represent a breakthrough in RA treatment. We aimed to investigate the effects of etanercept and adalimumab on human Th17-polarized cells and the possible intracellular regulators of these effects, including the Th17-specific transcription factors signal transducer, activator of transcription 3 (STAT3), retinoid-related orphan receptor γ-T (RORγt) and epigenetic modification...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27919786/increasing-in-cysteine-proteinase-b-expression-and-enzymatic-activity-during-in%C3%A2-vitro-differentiation-of-leishmania-viannia-braziliensis-first-evidence-of-modulation-during-morphological-transition
#20
Cinthia Bernardes Gomes, Franklin Souza -Silva, Karen Dos Santos Charret, Bernardo Acácio Santini Pereira, Léa Cysne Finkelstein, Raquel Santos-de-Souza, Luzia Monteiro de Castro Côrtes, Mirian Claudia Souza Pereira, Francisco Odêncio Rodrigues de Oliveira, Carlos Roberto Alves
Leishmania (Viannia) braziliensis presents adaptive protease-dependent mechanisms, as cysteine proteinases B (CPB). This study investigates the expression of three cpb gene isoforms and CPB enzymatic activity during the parasite differentiation. Relative expression levels of LbrM.08.0810 gene were assessed, exhibiting a higher quantity of transcripts in the logarithmic promastigotes phase than in the stationary promastigotes phase (>1.5 times). The cbp gene tends to decrease during acid pH shock and increases when the temperature rises (>1...
February 2017: Biochimie
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