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https://www.readbyqxmd.com/read/29321817/enhanced-myc-association-with-the-nua4-histone-acetyltransferase-complex-mediated-by-the-adenovirus-e1a-n-terminal-domain-activates-a-subset-of-myc-target-genes-highly-expressed-in-cancer-cells
#1
Ling-Jun Zhao, Paul M Loewenstein, Maurice Green
The proto-oncogene MYC is a transcription factor over-expressed in many cancers and required for cell survival. Its function is regulated by histone acetyltransferase (HAT) complexes, such as the GCN5 complex and the NuA4/Tip60 complex. However, the roles of the HAT complexes during MYC function in cancer have not been well characterized. We recently showed that adenovirus E1A and its N-terminal 80 aa region, E1A 1-80, interact with the NuA4 complex, through the E1A TRRAP-targeting (ET) domain, and enhance MYC association with the NuA4 complex...
November 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29311082/deletion-of-ada2-increases-antifungal-drug-susceptibility-and-virulence-in-candida-glabrata
#2
Shang-Jie Yu, Ya-Lin Chang, Ying-Lien Chen
Candida glabrata, the second most frequent cause of candidiasis after Candida albicans, is an emerging human fungal pathogen that is intrinsically drug tolerant. Currently, studies of C. glabrata genes involved in drug tolerance are limited. Ada2, a component serving as a transcription adaptor of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, is required for antifungal drug tolerance and virulence in C. albicans However, its roles in C. glabrata remain elusive. In this study, we found that ada2 mutants demonstrated severe growth defects at 40°C but only mild defects at 37°C or 25°C...
January 8, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29297932/inhibition-of-novel-gcn5-atm-axis-restricts-the-onset-of-acquired-drug-resistance-in-leukemia
#3
Sameer Salunkhe, Saket V Mishra, Jyothi Nair, Samadri Ghosh, Neha Choudhary, Ekjot Kaur, Sanket Shah, Ketaki Patkar, Dev Anand, Navin Khattry, Syed K Hasan, Shilpee Dutt
Leukemia is majorly treated by topoisomerase inhibitors that induce DNA double strand breaks (DSB) resulting in cell death. Consequently, modulation of DSB repair pathway renders leukemic cells resistant to therapy. Since we do not fully understand the regulation of DSB repair acquired by resistant cells, targeting these cells has been a challenge. Here we investigated the regulation of DSB repair pathway in Early Drug Resistant Population (EDRP) and Late Drug Resistant Population (LDRP). We found that doxorubicin induced equal DSBs in parent and EDRP cells however; cell death is induced only in the parent cells...
January 3, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29249668/gcn5-regulates-fgf-signaling-and-activates-selective-myc-target-genes-during-early-embryoid-body-differentiation
#4
Li Wang, Evangelia Koutelou, Calley Hirsch, Ryan McCarthy, Andria Schibler, Kevin Lin, Yue Lu, Collene Jeter, Jianjun Shen, Michelle C Barton, Sharon Y R Dent
Precise control of gene expression during development is orchestrated by transcription factors and co-regulators including chromatin modifiers. How particular chromatin-modifying enzymes affect specific developmental processes is not well defined. Here, we report that GCN5, a histone acetyltransferase essential for embryonic development, is required for proper expression of multiple genes encoding components of the fibroblast growth factor (FGF) signaling pathway in early embryoid bodies (EBs). Gcn5-/- EBs display deficient activation of ERK and p38, mislocalization of cytoskeletal components, and compromised capacity to differentiate toward mesodermal lineage...
December 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29241954/structural-characterization-of-ribt-from-bacillus-subtilis-reveals-it-as-a-gcn5-related-n-acetyltransferase
#5
Ritika Srivastava, Amanpreet Kaur, Charu Sharma, Subramanian Karthikeyan
In bacteria, biosynthesis of riboflavin occurs through a series of enzymatic steps starting with one molecule of GTP and two molecules of ribulose-5-phosphate. In Bacillus subtilis (B. subtilis) the genes (ribD/G, ribE, ribA, ribH and ribT) which are involved in riboflavin biosynthesis are organized in an operon referred as rib operon. All the genes of rib operon are characterized functionally except for ribT. The ribT gene with unknown function is found at the distal terminal of rib operon and annotated as a putative N-acetyltransferase...
December 11, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/29232376/che1-aatf-interacts-with-subunits-of-the-histone-acetyltransferase-core-module-of-saga-complexes
#6
Gizem Caliskan, Ikbal C Baris, Ferhan Ayaydin, Melanie J Dobson, Muge Senarisoy, Imre M Boros, Zeki Topcu, Sevil Zencir
General Control Non-derepressible 5 (GCN5) and Alteration/Deficiency in Activation 2 and 3 proteins (ADA2 and ADA3, respectively) are subunits of the Histone AcetylTransferase (HAT) module of SAGA- and ATAC-type co-activators. We previously reported four new interacting partners of human ADA3 identified by screening a human fetal brain cDNA library using yeast two hybrid technology. One of these partners was Apoptosis-Antagonizing Transcription Factor (AATF), also known as Che-1, an RNA polymerase II-binding protein with a number of roles in different cellular processes including regulation of transcription, cell proliferation, cell cycle control, DNA damage responses and apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/29211711/kat2a-coupled-with-the-%C3%AE-kgdh-complex-acts-as-a-histone-h3-succinyltransferase
#7
Yugang Wang, Yusong R Guo, Ke Liu, Zheng Yin, Rui Liu, Yan Xia, Lin Tan, Peiying Yang, Jong-Ho Lee, Xin-Jian Li, David Hawke, Yanhua Zheng, Xu Qian, Jianxin Lyu, Jie He, Dongming Xing, Yizhi Jane Tao, Zhimin Lu
Histone modifications, such as the frequently occurring lysine succinylation, are central to the regulation of chromatin-based processes. However, the mechanism and functional consequences of histone succinylation are unknown. Here we show that the α-ketoglutarate dehydrogenase (α-KGDH) complex is localized in the nucleus in human cell lines and binds to lysine acetyltransferase 2A (KAT2A, also known as GCN5) in the promoter regions of genes. We show that succinyl-coenzyme A (succinyl-CoA) binds to KAT2A...
December 14, 2017: Nature
https://www.readbyqxmd.com/read/29162325/scriptaid-improves-the-reprogramming-of-donor-cells-and-enhances-canine-porcine-interspecies-embryo-development
#8
Jin-Gu No, Tai-Young Hur, Minghui Zhao, Seunghoon Lee, Mi-Kyung Choi, Yoon-Seok Nam, Dong-Hyun Yeom, Gi-Sun Im, Dong-Hoon Kim
Histone methylation, histone acetylation, and DNA methylation are the important factors for somatic cell nuclear transfer (SCNT). Histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) have been used to improve cloning efficiency. In particular, scriptaid, an HDACi, has been shown to improve SCNT efficiency. However, no studies have been performed on canines. Here, we evaluated the effects of scriptaid on histone modification in canine ear fibroblasts (cEFs) and cloned canine embryos derived from cEFs...
November 18, 2017: Reproductive Biology
https://www.readbyqxmd.com/read/29141908/two-distinct-regulatory-mechanisms-of-transcriptional-initiation-in-response-to-nutrient-signaling
#9
Jannatul Ferdoush, Rwik Sen, Amala Kaja, Priyanka Barman, Sukesh R Bhaumik
SAGA (Spt-Ada-Gcn5-Acetyltransferase) and TFIID (transcription factor IID) have been previously shown to facilitate the PIC (pre-initiation complex) formation at the promoters of two distinct sets of genes. Here, we demonstrate that TFIID and SAGA differentially participate in stimulation of the PIC formation (and hence transcriptional initiation) at the promoter of PHO84, a gene for high affinity inorganic phosphate (Pi) transporter for crucial cellular functions, in response to nutrient signaling. We show that transcriptional initiation of PHO84 occurs predominantly in the TFIID-dependent manner in the absence of Pi in the growth medium...
November 15, 2017: Genetics
https://www.readbyqxmd.com/read/29111103/muscle-specific-knockout-of-general-control-of-amino-acid-synthesis-5-gcn5-does-not-enhance-basal-or-endurance-exercise-induced-mitochondrial-adaptation
#10
Jessica R Dent, Vitor F Martins, Kristoffer Svensson, Samuel A LaBarge, Noah C Schlenk, Mary C Esparza, Elisa H Buckner, Gretchen A Meyer, D Lee Hamilton, Simon Schenk, Andrew Philp
OBJECTIVE: Lysine acetylation is an important post-translational modification that regulates metabolic function in skeletal muscle. The acetyltransferase, general control of amino acid synthesis 5 (GCN5), has been proposed as a regulator of mitochondrial biogenesis via its inhibitory action on peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α). However, the specific contribution of GCN5 to skeletal muscle metabolism and mitochondrial adaptations to endurance exercise in vivo remain to be defined...
October 16, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29096064/a-mononuclear-iron-dependent-methyltransferase-catalyzes-initial-steps-in-assembly-of-the-apratoxin-a-polyketide-starter-unit
#11
Meredith A Skiba, Andrew P Sikkema, Nathan A Moss, Collin L Tran, Rebecca M Sturgis, Lena Gerwick, William H Gerwick, David H Sherman, Janet L Smith
Natural product biosynthetic pathways contain a plethora of enzymatic tools to carry out difficult biosynthetic transformations. Here, we discover an unusual mononuclear iron-dependent methyltransferase that acts in the initiation steps of apratoxin A biosynthesis (AprA MT1). Fe(3+)-replete AprA MT1 catalyzes one or two methyl transfer reactions on the substrate malonyl-ACP (acyl carrier protein), whereas Co(2+), Fe(2+), Mn(2+), and Ni(2+) support only a single methyl transfer. MT1 homologues exist within the "GNAT" (GCN5-related N-acetyltransferase) loading modules of several modular biosynthetic pathways with propionyl, isobutyryl, or pivaloyl starter units...
November 14, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28971961/integument-development-in%C3%A2-arabidopsis-depends-on-interaction-of-yabby-protein-inner-no-outer-with-co-activators-and-co-repressors
#12
Marissa K Simon, Debra J Skinner, Thomas L Gallagher, Charles S Gasser
Arabidopsis thaliana INNER NO OUTER (INO) is a YABBY protein that is essential for initiation and development of the outer integument of ovules. Other YABBY proteins have been shown to be involved in both negative and positive regulation of expression of putative target genes. YABBY proteins have also been shown to interact with the co-repressor LEUNIG (LUG) in several systems. In support of a repressive role for INO we confirm that INO interacts with LUG, and also find that INO directly interacts with SEUSS (SEU), a known co-repressive partner of LUG...
September 29, 2017: Genetics
https://www.readbyqxmd.com/read/28964624/sharing-the-saga
#13
REVIEW
Dominique Helmlinger, László Tora
Transcription initiation is a major regulatory step in eukaryotic gene expression. Co-activators establish transcriptionally competent promoter architectures and chromatin signatures to allow the formation of the pre-initiation complex (PIC), comprising RNA polymerase II (Pol II) and general transcription factors (GTFs). Many GTFs and co-activators are multisubunit complexes, in which individual components are organized into functional modules carrying specific activities. Recent advances in affinity purification and mass spectrometry analyses have revealed that these complexes often share functional modules, rather than containing unique components...
November 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28949514/identifying-dysregulated-epigenetic-enzyme-activity-in-castrate-resistant-prostate-cancer-development
#14
Jin-Hee Lee, Bing Yang, Anastasia J Lindahl, Nathan Damaschke, Melissa D Boersma, Wei Huang, Eva Corey, David F Jarrard, John M Denu
There is a tremendous need for novel strategies aimed at directly assessing activities of histone modifiers to probe epigenetic determinants associated with disease progression. Here, we developed a high-throughput peptide microarray assay to identify altered histone lysine (de)acetylation activity in prostate cancer (PCa). This microarray-based activity assay revealed up-regulated histone acetyltransferase (HAT) activity against specific histone H3 sites in a castrate-resistant (CR) PCa cell line compared to its hormone-sensitive (HS) isogenic counterpart...
November 17, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28947800/cytosolic-acetyl-coa-promotes-histone-acetylation-predominantly-at-h3k27-in-arabidopsis
#15
Chen Chen, Chenlong Li, Ying Wang, Justin Renaud, Gang Tian, Shrikaar Kambhampati, Behnaz Saatian, Vi Nguyen, Abdelali Hannoufa, Frédéric Marsolais, Ze-Chun Yuan, Kangfu Yu, Ryan S Austin, Jun Liu, Susanne E Kohalmi, Keqiang Wu, Shangzhi Huang, Yuhai Cui
Acetyl-coenzyme A (acetyl-CoA) is a central metabolite and the acetyl source for protein acetylation, particularly histone acetylation that promotes gene expression. However, the effect of acetyl-CoA levels on histone acetylation status in plants remains unknown. Here, we show that malfunctioned cytosolic acetyl-CoA carboxylase1 (ACC1) in Arabidopsis leads to elevated levels of acetyl-CoA and promotes histone hyperacetylation predominantly at lysine 27 of histone H3 (H3K27). The increase of H3K27 acetylation (H3K27ac) is dependent on adenosine triphosphate (ATP)-citrate lyase which cleaves citrate to acetyl-CoA in the cytoplasm, and requires histone acetyltransferase GCN5...
October 2017: Nature Plants
https://www.readbyqxmd.com/read/28943401/crystal-structure-of-l-glutamate-n-acetyltransferase-arga-from-mycobacterium-tuberculosis
#16
Xiuna Yang, Lijie Wu, Yajun Ran, Ao Xu, Bing Zhang, Xiaolin Yang, Rongguang Zhang, Zihe Rao, Jun Li
l-arginine is used as a source of both carbon and nitrogen in Mycobacterium tuberculosis (Mtb) and its biosynthesis is essential for the pathogen's survival. MtbArgA (Rv2747) catalyzes the initial step in l-arginine biosynthesis by transferring an acetyl group from acetyl coenzyme A (AcCoA) to l-glutamate. MtbArgA is a class III N-acetylglutamate synthase (NAGS) with no structural information. Here, we solved the crystal structure of MtbArgA complexed with AcCoA and l-glutamate. The overall structure adopts a classic fold of the GCN5-related N-acetyltransferase (GNAT) family, characterized by a "V"-shaped cleft and β-bulge, but uses distinct residues for the binding and reaction of AcCoA...
September 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28918903/saga-is-a-general-cofactor-for-rna-polymerase-ii-transcription
#17
Tiago Baptista, Sebastian Grünberg, Nadège Minoungou, Maria J E Koster, H T Marc Timmers, Steve Hahn, Didier Devys, László Tora
Prior studies suggested that SAGA and TFIID are alternative factors that promote RNA polymerase II transcription, with about 10% of genes in S. cerevisiae dependent on SAGA. We reassessed the role of SAGA by mapping its genome-wide location and role in global transcription in budding yeast. We find that SAGA maps to the UAS elements of most genes, overlapping with Mediator binding and irrespective of previous designations of SAGA- or TFIID-dominated genes. Disruption of SAGA through mutation or rapid subunit depletion reduces transcription from nearly all genes, measured by newly synthesized RNA...
October 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28900165/gcn5l1-modulates-cross-talk-between-mitochondria-and-cell-signaling-to-regulate-foxo1-stability-and-gluconeogenesis
#18
Lingdi Wang, Iain Scott, Lu Zhu, Kaiyuan Wu, Kim Han, Yong Chen, Marjan Gucek, Michael N Sack
The mitochondrial enriched GCN5-like 1 (GCN5L1) protein has been shown to modulate mitochondrial protein acetylation, mitochondrial content and mitochondrial retrograde signaling. Here we show that hepatic GCN5L1 ablation reduces fasting glucose levels and blunts hepatic gluconeogenesis without affecting systemic glucose tolerance. PEPCK and G6Pase transcript levels are downregulated in hepatocytes from GCN5L1 liver specific knockout mice and their upstream regulator, FoxO1 protein levels are decreased via proteasome-dependent degradation and via reactive oxygen species mediated ERK-1/2 phosphorylation...
September 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28887412/enzymatic-modules-of-the-saga-chromatin-modifying-complex-play-distinct-roles-in-drosophila-gene-expression-and-development
#19
Xuanying Li, Christopher W Seidel, Leanne T Szerszen, Jeffrey J Lange, Jerry L Workman, Susan M Abmayr
The Spt-Ada-Gcn5-acetyltransferase (SAGA) chromatin-modifying complex is a transcriptional coactivator that contains four different modules of subunits. The intact SAGA complex has been well characterized for its function in transcription regulation and development. However, little is known about the roles of individual modules within SAGA and whether they have any SAGA-independent functions. Here we demonstrate that the two enzymatic modules of Drosophila SAGA are differently required in oogenesis. Loss of the histone acetyltransferase (HAT) activity blocks oogenesis, while loss of the H2B deubiquitinase (DUB) activity does not...
August 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28854355/uv-induced-rpa1-acetylation-promotes-nucleotide-excision-repair
#20
Hanqing He, Jiajia Wang, Ting Liu
Replication protein A (RPA) is a multifunctional, single-stranded DNA-binding protein complex and plays a critical role in DNA replication and damage response. Herein, we show that the 70-kDa subunit of RPA (RPA1) is acetylated on lysine 163 by the acetyltransferases GCN5 and PCAF and that such acetylation is reversed principally via the action of the deacetylase HDAC6. UV irradiation promotes cytoplasmic translocation of HDAC6, thereby disrupting the interaction of HDAC6 with RPA1 and increasing RPA1 acetylation...
August 29, 2017: Cell Reports
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