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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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/the-iswi-atpase-smarca5-snf2h-is-required-for-proliferation-and-differentiation-of-hematopoietic-stem-and-progenitor-cells
#15
Juraj Kokavec, Tomas Zikmund, Filipp Savvulidi, Vojtech Kulvait, Winfried Edelmann, Arthur I Skoultchi, Tomas Stopka
The imitation switch 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
#16
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
#17
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
#18
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
#19
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
#20
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
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