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https://www.readbyqxmd.com/read/28790157/sirt7-and-the-dead-box-helicase-ddx21-cooperate-to-resolve-genomic-r-loops-and-safeguard-genome-stability
#1
Chenlin Song, Agnes Hotz-Wagenblatt, Renate Voit, Ingrid Grummt
R loops are three-stranded nucleic acid structures consisting of an RNA:DNA heteroduplex and a "looped-out" nontemplate strand. As aberrant formation and persistence of R loops block transcription elongation and cause DNA damage, mechanisms that resolve R loops are essential for genome stability. Here we show that the DEAD (Asp-Glu-Ala-Asp)-box RNA helicase DDX21 efficiently unwinds R loops and that depletion of DDX21 leads to accumulation of cellular R loops and DNA damage. Significantly, the activity of DDX21 is regulated by acetylation...
August 8, 2017: Genes & Development
https://www.readbyqxmd.com/read/28782640/effect-of-melatonin-on-neuronal-differentiation-requires-cbp-p300-mediated-acetylation-of-histone-h3-lysine-14
#2
Xian Li, Xueran Chen, Wenjuan Zhou, Shufang Ji, Xinyue Li, Guanchong Li, Guowei Liu, Fuwu Wang, Aijun Hao
The transition from multipotent neural stem cells (NSCs) to terminally differentiated neurons is a multistep process, and the transition is finely regulated by transcription factors with basic helix-loop-helix (bHLH) motifs. Melatonin is an endogenous neurohormone with profound neurotrophic and neuroprotective effects both during the embryonic developmental stage and adulthood. The effects of melatonin on the differentiation of NSCs have been reported, and these effects may be responsible for its neuroprotective properties...
August 3, 2017: Neuroscience
https://www.readbyqxmd.com/read/28768874/pgc1%C3%AE-transcriptional-adaptor-function-governs-hepatitis-b-virus-replication-by-controlling-hbcag-p21-protein-mediated-capsid-formation
#3
Rasha E Shalaby, Saira Iram, Bülent Çakal, Claudia E Oropeza, Alan McLachlan
In the human hepatoma cell line, Huh7, co-expression of the coactivators, peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α), cAMP responsive element binding protein binding protein (CBP), steroid receptor coactivator 1 (SRC1) and protein arginine methyltransferase 1 (PRMT1) only modestly increase HBV biosynthesis. However, utilizing the human embryonic kidney cell line, HEK293T, it was possible to demonstrate that PGC1α alone can support viral biosynthesis independently of additional coactivator or transcription factor expression...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28752224/early-preclinical-changes-in-hippocampal-creb-binding-protein-expression-in-a-mouse-model-of-familial-alzheimer-s-disease
#4
Miren Ettcheto, Sonia Abad, Dmitry Petrov, Ignacio Pedrós, Oriol Busquets, Elena Sánchez-López, Gemma Casadesús, Carlos Beas-Zarate, Eva Carro, Carme Auladell, Jordi Olloquequi, Merce Pallàs, Jaume Folch, Antoni Camins
The molecular basis of memory loss in Alzheimer's disease (AD), the main cause of senile dementia, is under investigation. In the present study, we have focused on the early hippocampal memory-related changes in APPswe/PS1dE9 (APP/PS1) mice, a well-established mouse model of familial AD. It is well known that molecules like cAMP response element binding (CREB) and binding protein (CBP) play a crucial role in memory consolidation. We analyzed CBP on its transcriptional activity and protein levels, finding a significant downregulation of both of them at 3-month-old mice...
July 27, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28751935/chk1-promotes-dna-damage-response-bypass-following-oxidative-stress-in-a-model-of-hydrogen-peroxide-associated-ulcerative-colitis-through-jnk-inactivation-and-chromatin-binding
#5
Kathrin Reissig, Andrew Silver, Roland Hartig, Antje Schinlauer, Diana Walluscheck, Thomas Guenther, Sandra Siedentopf, Jochen Ross, Diep-Khanh Vo, Albert Roessner, Angela Poehlmann-Nitsche
Dysregulation of c-Jun N-terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress. In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance. Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28740501/hac1-and-haf1-histone-acetyltransferases-have-different-roles-in-uv-b-responses-in-arabidopsis
#6
Julieta P Fina, Fiorella Masotti, Sebastián P Rius, Franco Crevacuore, Paula Casati
Arabidopsis has 12 histone acetyltransferases grouped in four families: the GNAT/HAG, the MYST/HAM, the p300/CBP/HAC and the TAFII250/HAF families. We previously showed that ham1 and ham2 mutants accumulated higher damaged DNA after UV-B exposure than WT plants. In contrast, hag3 RNA interference transgenic plants showed less DNA damage and lower inhibition of plant growth by UV-B, and increased levels of UV-B-absorbing compounds. These results demonstrated that HAM1, HAM2, and HAG3 participate in UV-B-induced DNA damage repair and signaling...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28713342/nf-%C3%AE%C2%BAbp50-and-hdac1-interaction-is-implicated-in-the-host-tolerance-to-infection-mediated-by-the-bacterial-quorum-sensing-signal-2-aminoacetophenone
#7
Arunava Bandyopadhaya, Amy Tsurumi, Laurence G Rahme
Some bacterial quorum sensing (QS) small molecules are important mediators of inter-kingdom signaling and impact host immunity. The QS regulated small volatile molecule 2-aminoacetophenone (2-AA), which has been proposed as a biomarker of Pseudomonas aeruginosa colonization in chronically infected human tissues, is critically involved in "host tolerance training" that involves a distinct molecular mechanism of host chromatin regulation through histone deacetylase (HDAC)1. 2-AA's epigenetic reprogramming action enables host tolerance to high bacterial burden and permits long-term presence of P...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28700938/golgi-outpost-synthesis-impaired-by-toxic-polyglutamine-proteins-contributes-to-dendritic-pathology-in-neurons
#8
Chang Geon Chung, Min Jee Kwon, Keun Hye Jeon, Do Young Hyeon, Myeong Hoon Han, Jeong Hyang Park, In Jun Cha, Jae Ho Cho, Kunhyung Kim, Sangchul Rho, Gyu Ree Kim, Hyobin Jeong, Jae Won Lee, TaeSoo Kim, Keetae Kim, Kwang Pyo Kim, Michael D Ehlers, Daehee Hwang, Sung Bae Lee
Dendrite aberration is a common feature of neurodegenerative diseases caused by protein toxicity, but the underlying mechanisms remain largely elusive. Here, we show that nuclear polyglutamine (polyQ) toxicity resulted in defective terminal dendrite elongation accompanied by a loss of Golgi outposts (GOPs) and a decreased supply of plasma membrane (PM) in Drosophila class IV dendritic arborization (da) (C4 da) neurons. mRNA sequencing revealed that genes downregulated by polyQ proteins included many secretory pathway-related genes, including COPII genes regulating GOP synthesis...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28680062/linking-functions-an-additional-role-for-an-intrinsically-disordered-linker-domain-in-the-transcriptional-coactivator-cbp
#9
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/28669924/histone-h3-lysine-4-methyltransferase-kmt2d
#10
REVIEW
Eugene Froimchuk, Younghoon Jang, Kai Ge
Histone-lysine N-methyltransferase 2D (KMT2D), also known as MLL4 and MLL2 in humans and Mll4 in mice, belongs to a family of mammalian histone H3 lysine 4 (H3K4) methyltransferases. It is a large protein over 5500 amino acids in size and is partially functionally redundant with KMT2C. KMT2D is widely expressed in adult tissues and is essential for early embryonic development. The C-terminal SET domain is responsible for its H3K4 methyltransferase activity and is necessary for maintaining KMT2D protein stability in cells...
September 5, 2017: Gene
https://www.readbyqxmd.com/read/28638460/zeb1-mediates-drug-resistance-and-emt-in-p300-deficient-crc
#11
Darina Lazarova, Michael Bordonaro
We discuss the hypothesis that ZEB1-Wnt-p300 signaling integrates epithelial to mesenchymal transition (EMT) and resistance to histone deacetylase inhibitors (HDACis) in colorectal cancer (CRC) cells. The HDACi butyrate, derived from dietary fiber, has been linked to CRC prevention, and other HDACis have been proposed as therapeutic agents against CRC. We have previously discussed that resistance to butyrate likely contributes to colonic carcinogenesis, and we have demonstrated that butyrate resistance leads to cross-resistance to cancer therapeutic HDACis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28627884/hydrogen-deuterium-exchange-mass-spectrometry-reveals-calcium-binding-properties-and-allosteric-regulation-of-downstream-regulatory-element-antagonist-modulator-dream
#12
Jun Zhang, Jing Li, Theodore A Craig, Rajiv Kumar, Michael L Gross
Downstream regulatory element antagonist modulator (DREAM) is an EF-hand Ca(2+)-binding protein that also binds to a specific DNA sequence, downstream regulatory elements (DRE), and thereby regulates transcription in a calcium-dependent fashion. DREAM binds to DRE in the absence of Ca(2+) but detaches from DRE under Ca(2+) stimulation, allowing gene expression. The Ca(2+) binding properties of DREAM and the consequences of the binding on protein structure are key to understanding the function of DREAM. Here we describe the application of hydrogen-deuterium exchange mass spectrometry (HDX-MS) and site-directed mutagenesis to investigate the Ca(2+) binding properties and the subsequent conformational changes of full-length DREAM...
July 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28625977/acetylation-of-mastermind-like-1-by-p300-drives-the-recruitment-of-nack-to-initiate-notch-dependent-transcription
#13
Ke Jin, Wen Zhou, Xiaoqing Han, Zhiqiang Wang, Bin Li, Shawn Jeffries, Wensi Tao, David J Robbins, Anthony J Capobianco
Although it has long been appreciated that p300 acts as a critical Notch coactivator, the mechanistic details of p300 in Notch-mediated transcription remain unclear. We previously demonstrated that PEAK1-related kinase activating pseudokinase 1 (NACK), also known as SGK223, is a critical coactivator of Notch signaling and binds to the Notch1 ternary complex. Herein we report that p300 and CBP acetylate Mastermind-like 1 (Maml1) on amino acid residues K188 and K189 to recruit NACK to the Notch1 ternary complex, which results in the recruitment of RNA polymerase II to initiate transcription...
June 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28616572/reversible-lysine-acetylation-regulates-nuclear-translocation-of-tyrrs-to-counteract-genotoxic-oxidative-stress
#14
Chaoqun Li, Wei Yu
Aminoacyl-tRNA synthetases, catalyzing the first step of protein synthesis, have been shown to involve with multiple additional physiologic responses. Here, we summarize our findings that p300/CBP-Associated Factor and Sirtuin 1 play the reversible acetylation role in regulating the nuclear translocation of Tyrosyl-tRNA synthetase and activating transcription factor E2F1, thus facilitating the repair of damaged DNA.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28589097/ago2-negatively-regulates-type-i-interferon-signaling-pathway-by-competition-binding-irf3-with-cbp-p300
#15
Shengyu Wang, Xin Sun, Chenyang Yi, Dan Zhang, Xian Lin, Xiaomei Sun, Huanchun Chen, Meilin Jin
Viral infection triggers a series of signaling cascades and host innate immune responses, including interferon (IFN) production, which depends on coordinated activity of multiple transcription factors. IFN regulatory factor 3 (IRF3) and transcriptional coactivator CREB binding protein (CBP) and/or p300 are core factors that participate in transcriptional complex formation in the nucleus. In general, cells balance the production of IFNs through suppressive and stimulative mechanisms, but viral infections can disrupt such equilibrium...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28580166/mof-as-an-evolutionarily-conserved-histone-crotonyltransferase-and-transcriptional-activation-by-histone-acetyltransferase-deficient-and-crotonyltransferase-competent-cbp-p300
#16
Xiaoguang Liu, Wei Wei, Yuting Liu, Xueli Yang, Jian Wu, Yang Zhang, Qiao Zhang, Tieliu Shi, James X Du, Yingming Zhao, Ming Lei, Jin-Qiu Zhou, Jiwen Li, Jiemin Wong
Recent studies indicate that histones are subjected to various types of acylation including acetylation, propionylation and crotonylation. CBP and p300 have been shown to catalyze multiple types of acylation but are not conserved in evolution, raising the question as to the existence of other enzymes for histone acylation and the functional relationship between well-characterized acetylation and other types of acylation. In this study, we focus on enzymes catalyzing histone crotonylation and demonstrate that among the known histone acetyltransferases, MOF, in addition to CBP and p300, also possesses histone crotonyltransferase (HCT) activity and this activity is conserved in evolution...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28576496/identification-of-zinc-finger-transcription-factor-egr2-as-a-novel-acetylated-protein
#17
Kota Noritsugu, Akihiro Ito, Yoichi Nakao, Minoru Yoshida
EGR2 is a zinc finger transcription factor that regulates myelination in the peripheral nervous system and T cell anergy. The transcriptional activity of EGR2 is known to be regulated by its co-activators and/or co-repressors. Although the activity of transcription factors is generally regulated not only by interactions with co-regulators but also posttranslational modifications including acetylation, little is known about posttranslational modifications of EGR2. Here we show that EGR2 is a novel acetylated protein...
May 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28547133/hsf1-acetylation-decreases-its-transcriptional-activity-and-enhances-glucolipotoxicity-induced-apoptosis-in-rat-and-human-beta-cells
#18
Indri Purwana, Jun J Liu, Bernard Portha, Jean Buteau
AIMS/HYPOTHESIS: Heat shock factor protein 1 (HSF1) is a transcription factor that regulates the expression of key molecular chaperones, thereby orchestrating the cellular response to stress. This system was recently implicated in the control of insulin sensitivity and is therefore being scrutinised as a novel therapeutic avenue for type 2 diabetes. However, the regulation and biological actions of HSF1 in beta cells remain elusive. Herein, we sought to investigate the regulation of HSF1 in pancreatic beta cells and to study its potential role in cell survival...
May 25, 2017: Diabetologia
https://www.readbyqxmd.com/read/28534508/utx-promotes-hormonally-responsive-breast-carcinogenesis-through-feed-forward-transcription-regulation-with-estrogen-receptor
#19
G Xie, X Liu, Y Zhang, W Li, S Liu, Z Chen, B Xu, J Yang, L He, Z Zhang, T Jin, X Yi, L Sun, Y Shang, J Liang
UTX is implicated in embryonic development and lineage specification. However, how this X-linked histone demethylase contributes to the occurrence and progression of breast cancer remains to be clarified. Here we report that UTX is physically associated with estrogen receptor (ER) and functions in ER-regulated transcription. We showed that UTX coordinates with JHDM1D and CBP to direct H3K27 methylation-acetylation transition and to create a permissive chromatin state on ER targets. Genome-wide analysis of the transcriptional targets of UTX by ChIP-seq identified a set of genes such as chemokine receptor CXCR4 that are intimately involved in breast cancer tumorigenesis and metastasis...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28523540/rubinstein-taybi-syndrome-and-epigenetic-alterations
#20
Edward Korzus
Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder in humans characterized by growth and psychomotor delay, abnormal gross anatomy, and mild to severe mental retardation (Rubinstein and Taybi, Am J Dis Child 105:588-608, 1963, Hennekam et al., Am J Med Genet Suppl 6:56-64, 1990). RSTS is caused by de novo mutations in epigenetics-associated genes, including the cAMP response element-binding protein (CREBBP), the gene-encoding protein referred to as CBP, and the EP300 gene, which encodes the p300 protein, a CBP homologue...
2017: Advances in Experimental Medicine and Biology
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