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https://www.readbyqxmd.com/read/28523540/rubinstein-taybi-syndrome-and-epigenetic-alterations
#1
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
https://www.readbyqxmd.com/read/28513807/the-nuclear-pore-protein-nup153-associates-with-chromatin-and-regulates-cardiac-gene-expression-in-dystrophic-mdx-hearts
#2
Simona Nanni, Agnese Re, Cristian Ripoli, Aoife Gowran, Patrizia Nigro, Domenico D'Amario, Antonio Amodeo, Filippo Crea, Claudio Grassi, Alfredo Pontecorvi, Antonella Farsetti, Claudia Colussi
Aims: Beyond the control of nuclear-cytoplasmic trafficking nucleoporins regulate gene expression and are involved in cardiac diseases. Notably, a number of cardiovascular disorders have been linked to alterations in epigenetic mechanisms. Here we aimed to determine the contribution of Nup153 to the epigenetic alterations occurring in cardiomyopathy of dystrophin-deficient mdx mice (C57BL/10ScSn-Dmd mdx /J). Methods and results: Nup153 was lysine-acetylated and its expression was significantly increased at protein level in mdx hearts compared with controls...
November 1, 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/28501104/knockdown-of-cbp-p300-interacting-transactivator-with-glu-asp-rich-carboxy-terminal-domain-2-inhibits-cell-division-and-increases-apoptosis-in-gastric-cancer
#3
Ze Tang, Gan He, Jie Xu, Li Zhongfu
BACKGROUND: Cbp/P300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2) is a pleiotropic protein associated with numerous cell functions, including transcription and differentiation. The role of CITED2 has been investigated in a number of malignancies; however, the roles of this protein in gastric cancers remain unclear. Therefore, we determined the role of CITED2 in gastric cancers. MATERIALS AND METHODS: Gastric cancer cell lines (MKN74, MKN28, 7901, and AGS) were used to assess CITED2 transcript levels...
May 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28488757/stimulation-of-pol-iii-dependent-5s-rrna-and-u6-snrna-gene-expression-by-ap-1-transcription-factors
#4
Richa Ahuja, Vijay Kumar
RNA polymerase III transcribes structurally diverse group of essential non-coding RNAs including 5S rRNA and U6 snRNA. These non-coding RNAs are involved in RNA processing and ribosome biogenesis, thus, coupling Pol III activity to the rate of protein synthesis, cell growth and proliferation. Even though a few Pol II-associated transcription factors have been reported to participate in Pol III-dependent transcription, its activation by AP-1 factors c-Fos and c-Jun has remained unexplored. Here, we show that c-Fos and c-Jun bind to specific sites in the regulatory regions of 5S rRNA (type I) and U6 snRNA (type III) gene promoters and stimulate their transcription...
May 10, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28474232/ets-targeted-therapy-can-it-substitute-for-mek-inhibitors
#5
REVIEW
Osamu Tetsu, Frank McCormick
BACKGROUND: The RAS/MAPK pathway has been intensively studied in cancer. Constitutive activation of ERK1 and ERK2 is frequently found in cancer cells from a variety of tissues. In clinical practice and clinical trials, small molecules targeting receptor tyrosine kinases or components in the MAPK cascade are used for treatment. MEK1 and MEK2 are ideal targets because these enzymes are physiologically important and have narrow substrate specificities and distinctive structural characteristics...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28460484/the-%C3%AE-catenin-cbp-antagonist-icg-001-inhibits-pediatric-glioma-tumorigenicity-in-a-wnt-independent-manner
#6
Maria Wiese, Neele Walther, Christopher Diederichs, Fabian Schill, Sebastian Monecke, Gabriela Salinas, Dominik Sturm, Stefan M Pfister, Ralf Dressel, Steven A Johnsen, Christof M Kramm
Pediatric high-grade gliomas (pedHGG) belong to the most aggressive cancers in children with a poor prognosis due to a lack of efficient therapeutic strategies. The β-catenin/Wnt-signaling pathway was shown to hold promising potential as a treatment target in adult high-grade gliomas by abrogating tumor cell invasion and the acquisition of stem cell-like characteristics. Since pedHGG differ from their adult counterparts in genetically and biologically we aimed to investigate the effects of β-catenin/Wnt-signaling pathway-inhibition by the β-catenin/CBP antagonist ICG-001 in pedHGG cell lines...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28442062/retinoic-acid-triggers-c-kit-gene-expression-in-spermatogonial-stem-cells-through-an-enhanceosome-constituted-between-transcription-factor-binding-sites-for-retinoic-acid-response-element-rare-spleen-focus-forming-virus-proviral-integration-oncogene-spfi1-pu
#7
Swanand Koli, Ayan Mukherjee, Kudumula Venkata Rami Reddy
Restricted availability of retinoic acid (RA) in the testicular milieu regulates transcriptional activity of c-kit (KIT, CD117), which aids in the determination of spermatogonial stem-cell differentiation. The effect of RA on c-kit has been reported previously, but its mode of genomic action remains unresolved. We studied the molecular machinery guiding RA responsiveness to the c-kit gene using spermatogonial stem-cell line C18-4 and primary spermatogonial cells. A novel retinoic acid response element (RARE) positioned at -989 nucleotides upstream of the transcription start site (TSS) was identified, providing a binding site for a dimeric RA receptor (i...
March 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28416608/hyper-o-glcnacylation-activates-nf-%C3%AE%C2%BAb-signaling-through-interplay-with-phosphorylation-and-acetylation
#8
Zhiyuan Ma, Robert J Chalkley, Keith Vosseller
O-GlcNAcylation is the covalent addition of an O-linked β-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. O-GlcNAcylation, analogous to phosphorylation, plays critical roles in gene expression through direct modification of transcription factors such as NF-κB. Aberrantly increased NF-κB O-GlcNAcylation has been linked to NF-κB constitutive activation and cancer development. Therefore, it is of a great biological and clinical significance to dissect the molecular mechanisms that tune NF-κB activity...
April 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28410781/virtual-screen-to-nmr-vs2nmr-discovery-of-fragment-hits-for-the-cbp-bromodomain
#9
Dimitrios Spiliotopoulos, Jian Zhu, Eike-Christian Wamhoff, Nicholas Deerain, Jean-Rémy Marchand, Jonas Aretz, Christoph Rademacher, Amedeo Caflisch
Overexpression of the CREB-binding protein (CBP), a bromodomain-containing transcription coactivator involved in a variety of cellular processes, has been observed in several types of cancer with a correlation to aggressiveness. We have screened a library of nearly 1500 fragments by high-throughput docking into the CBP bromodomain followed by binding energy evaluation using a force field with electrostatic solvation. Twenty of the 39 fragments selected by virtual screening are positive in one or more ligand-observed nuclear magnetic resonance (NMR) experiments...
April 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28398509/mll3-mll4-are-required-for-cbp-p300-binding-on-enhancers-and-super-enhancer-formation-in-brown-adipogenesis
#10
Binbin Lai, Ji-Eun Lee, Younghoon Jang, Lifeng Wang, Weiqun Peng, Kai Ge
Histone H3K4me1/2 methyltransferases MLL3/MLL4 and H3K27 acetyltransferases CBP/p300 are major enhancer epigenomic writers. To understand how these epigenomic writers orchestrate enhancer landscapes in cell differentiation, we have profiled genomic binding of MLL4, CBP, lineage-determining transcription factors (EBF2, C/EBPβ, C/EBPα, PPARγ), coactivator MED1, RNA polymerase II, as well as epigenome (H3K4me1/2/3, H3K9me2, H3K27me3, H3K36me3, H3K27ac), transcriptome and chromatin opening during adipogenesis of immortalized preadipocytes derived from mouse brown adipose tissue (BAT)...
April 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28387959/high-quality-genome-assembly-of-capsella-bursa-pastoris-reveals-asymmetry-of-regulatory-elements-at-early-stages-of-polyploid-genome-evolution
#11
Artem S Kasianov, Anna V Klepikova, Ivan V Kulakovskiy, Evgeny S Gerasimov, Anna V Fedotova, Elizaveta G Besedina, Alexey S Kondrashov, Maria D Logacheva, Aleksey A Penin
Polyploidization and subsequent sub- and neofunctionalization of duplicated genes represent a major mechanism of plant genome evolution. Capsella bursa-pastoris, a widespread ruderal plant, is a recent allotetraploid, and, thus, is an ideal model organism for studying early changes following polyploidization. We constructed a high-quality assembly of C. bursa-pastoris genome and a transcriptome atlas covering a broad sample of organs and developmental stages (available online at http://travadb.org/browse/Species=Cbp)...
April 7, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28387346/plk1-regulates-the-repressor-function-of-foxm1b-by-inhibiting-its-interaction-with-the-retinoblastoma-protein
#12
Nishit K Mukhopadhyay, Vaibhav Chand, Akshay Pandey, Dragana Kopanja, Janai R Carr, Yi-Ju Chen, Xiubei Liao, Pradip Raychaudhuri
FoxM1b is a cell cycle-regulated transcription factor, whose over-expression is a marker for poor outcome in cancers. Its transcriptional activation function requires phosphorylation by Cdk1 or Cdk2 that primes FoxM1b for phosphorylation by Plk1, which triggers association with the co-activator CBP. FoxM1b also possesses transcriptional repression function. It represses the mammary differentiation gene GATA3 involving DNMT3b and Rb. We investigated what determines the two distinct functions of FoxM1b: activation and repression...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28383551/p45-nf-e2-regulates-syncytiotrophoblast-differentiation-by-post-translational-gcm1-modifications-in-human-intrauterine-growth-restriction
#13
Shrey Kohli, Juliane Hoffmann, Franziska Lochmann, Paulina Markmeyer, Hanna Huebner, Fabian B Fahlbusch, Moh'd Mohanad Al-Dabet, Ihsan Gadi, Jayakumar Manoharan, Michael Löttge, Ana C Zenclussen, Anat Aharon, Benjamin Brenner, Khurrum Shahzad, Matthias Ruebner, Berend Isermann
Placental insufficiency jeopardizes prenatal development, potentially leading to intrauterine growth restriction (IUGR) and stillbirth. Surviving fetuses are at an increased risk for chronic diseases later in life. IUGR is closely linked with altered trophoblast and placental differentiation. However, due to a paucity of mechanistic insights, suitable biomarkers and specific therapies for IUGR are lacking. The transcription factor p45 NF-E2 (nuclear factor erythroid derived 2) has been recently found to regulate trophoblast differentiation in mice...
April 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28358424/exome-sequencing-reveals-novel-irxi-mutation-in-congenital-heart-disease
#14
Changlong Guo, Qidi Wang, Yuting Wang, Liping Yang, Haiyan Luo, Xiao Fang Cao, Lisha An, Yue Qiu, Meng Du, Xu Ma, Hui Li, Cailing Lu
Genetic variation in specific transcription factors during heart formation may lead to congenital heart disease (CHD) or even miscarriage. The aim of the present study was to identify CHD‑associated genes using next generation sequencing (NGS). The whole exome DNA sequence was obtained from a stillborn fetus diagnosed with tricuspid atresia and complete transposition of the great arteries using high‑throughput sequencing methods. Subsequently, genetic variants of CHD‑associated genes were selected and verified in 215 non‑syndromic CHD patients and 249 healthy control subjects using polymerase chain reaction combined with Sanger sequencing...
May 2017: Molecular Medicine Reports
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
#15
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...
May 19, 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
#16
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
#17
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
#18
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). Whereas KEAP1-dependent regulation is a major determinant of NRF2 activity, NRF2-mediated transcriptional activation varies from context to context, suggesting that other intracellular signaling cascades may impact NRF2 function...
May 5, 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
#19
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
#20
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
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