Abstract
We found that thapsigargin-induced ER stress augmented recruitment of IFN regulatory factor-3, CREB binding protein/p300, and transcriptional machinery to the murine ifnb1 promoter during LPS stimulation. Although full synergistic IFN-beta production requires X-box binding protein 1 (XBP-1), this UP...
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PMID: 20660350
PDF is available here.
Abstract
We have previously shown that all-trans retinoic acid (atRA), a bioactive metabolite of vitamin A, significantly augmented DC MMP-9 mRNA and protein production. We investigated the mechanisms by which atRA increased MMP-9 activity in vitro. Mouse myeloid DC cultured with atRA demonstrated increased...
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PMID: 20534877
PDF is available here.
Abstract
We used microarray analyses to examine gene expression profiles in the context of bone marrow-derived macrophages overexpressing a constitutively active form of NFATc1. Herein, we demonstrate that MHC class II transactivator (CIITA) is up-regulated downstream of NFATc1. Overexpression of CIITA in os...
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PMID: 20466061
PDF is available here.
Abstract
We demonstrate that ERRalpha interacts with and is acetylated by p300 coactivator associated factor (PCAF) in vitro and in mouse liver. Purified PCAF acetylated the DNA-binding domain of ERRalpha on four highly-conserved lysines. In addition, coexpression of PCAF reduced the transcriptional activity...
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PMID: 20484414
PDF is available here.
Abstract
We found that SIRT1 binds to HIF-1alpha and deacetylates it at Lys674, which is acetylated by PCAF. By doing so, SIRT1 inactivated HIF-1alpha by blocking p300 recruitment and consequently repressed HIF-1 target genes. During hypoxia, SIRT1 was downregulated due to decreased NAD(+) levels, which allo...
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PMID: 20620956
PDF is available here.
Abstract
We find that many genes involved in angiogenesis such as FLT-1, KDR, and angiopoietin 2 have potential E2F1 binding sites in their promoter. Chromatin immunoprecipitation (ChIP) assays showed that E2F1 can associate with these promoters and the recruitment of E2F1 was enhanced upon vascular endothel...
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PMID: 20516113
PDF is available here.
Abstract
We have previously shown that two HAT genes, Clock and Tip60, are overexpressed, and upregulate glutathione biosynthesis and the expression of DNA repair genes in cisplatin-resistant cells. To better understand the mechanism of HAT-related drug resistance, we investigated the role of another HAT gen...
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PMID: 20530585
PDF is available here.
Abstract
We showed that NF-kappaB/p52 can activate the AR, resulting in increased transactivation of AR-responsive genes, such as PSA and NKX3.1, in a ligand-independent manner. NF-kappaB2/p52 enhances nuclear translocation and activation of AR by interacting with its NH(2)-terminal domain and enhances the r...
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PMID: 20388792
PDF is available here.
Abstract
We found that Egr-1 mediates extracellular signal-regulated kinase and c-jun NH(2)-terminal kinase mitogen-activated protein kinase-dependent MMP-9 transcription on TNFalpha stimulation. The requirement for Egr-1 in MMP-9 expression is further supported by the fact that HeLa cells expressing Egr-1 s...
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PMID: 20332214
PDF is available here.
Abstract
We described the characterization of a novel viral protein that we have termed HBZ for HTLV-1 bZIP factor. This viral factor is encoded on the antisense strand of HTLV-1 proviral DNA, demonstrating the existence of antisense transcription from a promoter located in the 3' LTR. HBZ can negatively con...
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PMID: 20412744
PDF is available here.
Alexander Köenig,
Thomas Linhart,
Katrin Schlengemann,
Kristina Reutlinger,
Jessica Wegele,
Guido Adler,
Garima Singh,
Leonie Hofmann,
Steffen Kunsch,
Thomas Büch,
Eva Schäfer,
Thomas M Gress,
Martin E Fernandez-Zapico and
Volker Ellenrieder
Abstract
Our study uncovers a novel mechanism regulating cell growth and identifies the NFAT/ELK complex as modulators of early stages of mitogen-stimulated proliferation in pancreatic cancer cells.
Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved....
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PMID: 19900447
PDF is available here.
Abstract
We demonstrated that the acetyltransferase p300/CBP associated factor (PCAF) functions as a negative regulator of FOXO1. We showed that PCAF bound to the forkhead domain of FOXO1 and acetylated FOXO1 at the K242 and K245 residues. However, PCAF repressed FOXO1-induced transcription in an enzymatic a...
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PMID: 20041807
PDF is available here.
Abstract
We review the status of cyclin A degradation in the light of recent evidence indicating that acetylation plays a role in cyclin A stability. The emerging model proposes that the acetyltransferase PCAF [p300/CREB (cAMP-response-element-binding protein)-binding protein-associated factor] [perhaps also...
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PMID: 20074040
PDF is available here.
Abstract
One general principle of gene regulation is that DNA-binding transcription factors modulate transcription by recruiting cofactors that modify histones and chromatin structure. A second implicit principle is that a particular cofactor is necessary at all the target genes where the cofactor is recruit...
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PMID: 20110770
PDF is available here.
Abstract
We identify a key lysine residue in the nuclear export signal of Sox2 that is acetylated, and demonstrate that blocking acetylation at this site retains Sox2 in the nucleus and sustains expression of its target genes under hyperacetylation or differentiation conditions. Mimicking acetylation at this...
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PMID: 19591226
PDF is available here.
Abstract
We found that MRFs (myogenic regulatory factors) regulated the expression of PGC-1alpha (peroxisome-proliferator-activated receptor gamma co-activator 1alpha) by targeting a short region, from nt -49 to +2 adjacent to the transcription initiation site, that contained two E-boxes. However, only the E...
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PMID: 19522704
PDF is available here.
Abstract
We investigated the effect of p53 on the expression and function of TFF2 in gastric cancer cell lines. Gene expression was determined by reverse transcription-polymerase chain reaction, and promoter activity was assessed by dual luciferase reporter assays. Apoptosis was detected by flow cytometry, a...
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PMID: 19541923
PDF is available here.
Abstract
We describe a highly purified system that allows for efficient activator-dependent transcription by RNA polymerase II from the promoter through several contiguous nucleosomes on defined chromatin templates. The system contains natural or recombinant histones, chromatin assembly factors, the histone-...
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PMID: 19272450
PDF is available here.
Abstract
I discuss the latest contributions to understanding the roles of the SAGA complex, highlighting the characterization of the SAGA-deubiquitination module, and emphasizing the functions newly ascribed to SAGA during transcription elongation and messenger-RNA export. These findings suggest that a cross...
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PMID: 19609321
PDF is available here.
Abstract
We find that increased NF-kappaB activation cannot explain the elevated IL8 expression and promoter acetylation seen in CFTR-deficient cells. Recognized components of the NF-kappaB-coactivator complex, acetyltransferase CBP, p300, and the histone deacetylase HDAC1, are unchanged by CFTR activity. Ho...
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PMID: 19411311
PDF is available here.
Abstract
We characterized the interactions of KLF5 with other transcription factors and promoter DNA elements in the context of TGFbeta. KLF5 interacted with Smad2-4 and Miz-1 in a TGFbeta-independent manner, but interacted with Myc only when TGFbeta was activated, and at least some of the interactions had a...
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PMID: 19419955
PDF is available here.
Abstract
We investigated the molecular mechanism of HDAC inhibitor induction of P-gp expression. HDAC inhibitor treatment causes cell type-specific induction of P-gp expression without changes in the CpG methylation status of the promoter region. In addition, our data show that HDAC inhibitor does not alter...
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PMID: 19435809
PDF is available here.
Abstract
We purified SUMO-1-conjugated p53 (Su-p53) to near homogeneity. Su-p53 exists in solution as a tetramer and interacts with p300 histone acetyltransferase as efficiently as the unmodified protein. Nevertheless, it fails to activate p53-dependent chromatin transcription because of its inability to bin...
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PMID: 19339993
PDF is available here.
Abstract
We show that, in late G1 and early S phase, CDC6 is found in a complex also containing Cyclin A, cyclin-dependent kinase (CDK)-2 and the acetyltransferase general control nonderepressible 5 (GCN5). GCN5 specifically acetylates CDC6 at three lysine residues flanking its cyclin-docking motif, and this...
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PMID: 19343071
PDF is available here.
Abstract
We report that the tumor suppressor p53 and its acetyltransferases CBP/p300 form a transcriptional complex that regulates the axonal growth-associated protein 43, a well-characterized pro-axon outgrowth and regeneration protein. Acetylated p53 at K372-3-82 drives axon outgrowth, GAP-43 expression, a...
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PMID: 19057620
PDF is available here.
Abstract
Of the 15 cases, 10 showed good histological responses to MPA (Responder) and 5 poor responses (Non-responder). In Responders, MPA treatment resulted in reduced expression of Ki-67 by 78% (p=0.0076) along with increased NCoR expression by 158 % (p=0.0077). Progestin treatment for T47D cells resulted...
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PMID: 19414341
PDF is available here.
Axel Visel,
Matthew J Blow,
Zirong Li,
Tao Zhang,
Jennifer A Akiyama,
Amy Holt,
Ingrid Plajzer-Frick,
Malak Shoukry,
Crystal Wright,
Feng Chen,
Veena Afzal,
Bing Ren,
Edward M Rubin and
Len A Pennacchio
Abstract
We present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue. We tested 86 of these sequences in a transgenic...
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PMID: 19212405
PDF is available here.
Abstract
We attempted to understand the mechanism of regulation of hHRI expression in the lead- and hemin-exposed cells. Our results demonstrate the involvement of two transcription factors, Elk-1 and MZF-1 in regulating HRI expression. Chromatin immunoprecipitation assays established further that Elk-1 is i...
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PMID: 19133234
PDF is available here.
Abstract
We have previously shown that Chk2 stability, which is increased after DNA damage in some cells, is regulated in part through phosphorylation at S456 and that a mutant Chk2 (S456A) is hyperubiquitinated and turned over more rapidly than wild-type Chk2.(1) Here we show that the S456A mutant preferent...
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PMID: 19176998
PDF is available here.
Abstract
We show that CREB-binding protein (CBP)/p300-interacting transactivator with ED-rich tail 2 (Cited2), which binds to the cysteine-histidine-rich region 1 of p300 and CBP, regulates muscle mass in vitro. Adenovirus-mediated overexpression of wild-type Cited2 significantly blocked morphological altera...
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PMID: 19032942
PDF is available here.
Abstract
Mutations in each of the transcriptional co-activator genes - CBP, p300, Cited2, Cart1 and Carm1 - result in neural tube defects in mice. The present study thus furnishes a complete and comparative temporal and spatial expression map of CBP/p300 and associated transcriptional co-activators, Cited2,...
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PMID: 19598128
PDF is available here.
Abstract
We report identification of the first three in vivo non-histone protein substrates of lysine propionylation in eukaryotic cells: p53, p300, and CREB-binding protein. We used mass spectrometry to map lysine propionylation sites within these three proteins. We also identified the first two in vivo euk...
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PMID: 18753126
PDF is available here.
Abstract
We report that ADA2a and ADA2b, two human homologues of yeast Ada2, each have the ability to form a heterotrimer with ADA3 and GCN5L but that only the ADA2b homologue is found in STAGA. By comparing the patterns of acetylation of several substrates, we found context-dependent requirements for ADA2b...
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PMID: 18936164
PDF is available here.
Abstract
We previously reported that trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, induced DLC-1 mRNA expression and accumulated acetylated histones H3 and H4 associated with the DLC-1 promoter in DLC-1 non-expressing gastric cancer cells. In this study, we demonstrated the molecular mechanis...
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PMID: 19116449
PDF is available here.
Abstract
We show that DMC and BDMC suppressed CRT that was activated by Wnt3a conditioned-medium (Wnt3a-CM) without altering the level of intracellular beta-catenin, and inhibited the growth of various colon cancer cells, with comparable potency to curcumin. Additionally, DMC and BDMC down-regulated p300, wh...
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PMID: 19000900
PDF is available here.
Abstract
We investigated the effect of Tcl1 expression on NF-kappaB and activator protein 1 (AP-1) activity. We found that Tcl1 physically interacts with c-Jun, JunB, and c-Fos and inhibits AP-1 transcriptional activity. Additionally, Tcl1 activates NF-kappaB by physically interacting with p300/CREB binding...
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PMID: 19064921
PDF is available here.
Abstract
We show that, by acting at the membrane, Tat induces IL-10 expression in primary monocytes and promonocytic U937 cells by NF-kappaB-dependent pathways. The trans-dominant negative mutants of NF-kappaB-inducing kinase (NIK), IKKalpha and IKKbeta expressed in our transactivation model, in accordance w...
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PMID: 18760861
PDF is available here.
Abstract
We purified the PML complex and identified Fbxo3 (Fbx3), Skp1, and Cullin1 as novel components of this complex. Fbx3 formed SCF(Fbx3) ubiquitin ligase and promoted the degradation of HIPK2 and p300 by the ubiquitin-proteasome pathway. PML inhibited this degradation through a mechanism that unexpecte...
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PMID: 18809579
PDF is available here.
Abstract
We here found that YC-1 acts in a novel manner to inhibit HIF-1. In the Gal4 reporter system, which is not degraded by YC-1, YC-1 was found to significantly inactivate the COOH-terminal transactivation domain (CAD) of HIF-1alpha, whereas it failed to inactivate CAD(N803A) mutant. In coimmunoprecipit...
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PMID: 19074848
PDF is available here.
Abstract
All vertebrate animals have developed a sophisticated regulatory system to cope with frequent and unpredictable episodes of fasting. A recent letter to Nature suggests that a switch from early gluconeogenic gene activation via CRTC2 (also known as TORC2) to late action of FOXO1 is cr...
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PMID: 19041759
PDF is available here.
Abstract
We now report the purification and characterization of vertebrate (human) ATAC-type complexes and identify novel components of STAGA. We show that human ATAC complexes incorporate in addition to GCN5 or PCAF (GCN5/PCAF), other epigenetic coregulators (ADA2-A, ADA3, STAF36, and WDR5), cofactors of ch...
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PMID: 18838386
PDF is available here.
Abstract
We investigated the role of multiple co-activators in regulating MMP-9 transcription. We demonstrate that multiple transcriptional co-activators are involved in MMP-9 promoter activation, including CBP/p300, PCAF, CARM1 and GRIP1. Furthermore, enhancement of MMP-9 promoter activity requires the hist...
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PMID: 18790699
PDF is available here.
Yi Liu,
Renaud Dentin,
Danica Chen,
Susan Hedrick,
Kim Ravnskjaer,
Simon Schenk,
Jill Milne,
David J Meyers,
Phil Cole,
John Yates,
Jerrold Olefsky,
Leonard Guarente and
Marc Montminy
Abstract
We show that a fasting-inducible switch, consisting of the histone acetyltransferase p300 and the nutrient-sensing deacetylase sirtuin 1 (SIRT1), maintains energy balance in mice through the sequential induction of CRTC2 and FOXO1. After glucagon induction, CRTC2 stimulated gluconeogenic gene expres...
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PMID: 18849969
PDF is available here.
Abstract
We characterized here the mechanisms through which the coactivator SRC-3 controls energy homeostasis. SRC-3 knock-out mice present a more favorable metabolic profile relative to their wild-type littermates. This metabolic improvement in SRC-3(-/-) mice is caused by an increase in mitochondrial funct...
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PMID: 18957541
PDF is available here.
Abstract
We found that the NAD(+)-dependent histone deacetylase SIRT2 deacetylates p300 in vitro and in cells. SIRT2 deacetylates lysine residues in the catalytic domain of p300 and restores binding of p300 to the PIC. RNAi-mediated depletion or chemical inhibition of SIRT2 in cells results in accumulation o...
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PMID: 18995842
PDF is available here.
Abstract
We investigated the function of the STAT3 NH(2)-terminal domain and how its interaction with p300 regulates STAT3 signal transduction. In STAT3(-/-) mouse embryonic fibroblasts, a stably expressed NH(2) terminus-deficient STAT3 mutant (STAT3-DeltaN) was unable to efficiently induce either STAT3-medi...
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PMID: 18782771
PDF is available here.
Abstract
We report that p300 interacts with Sirt2, a member of the Sir2 family, and triggers the acetylation and subsequent down-regulation of the deacetylation activity of Sirt2, and that the acetylation of Sirt2 by p300 relieves the inhibitory effect of Sirt2 on the transcriptional activity of p53. These o...
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PMID: 18722353
PDF is available here.
Abstract
We show that interaction with PEBP2-beta leads to the phosphorylation of RUNX1, which in turn induces p300 phosphorylation. This is mediated by homeodomain interacting kinase 2 (HIPK2), targeting Ser(249), Ser(273), and Thr(276) in RUNX1, in a manner that is also dependent on the RUNX1 PY motif. Imp...
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PMID: 18695000
PDF is available here.
Abstract
We show that CSB mutant cells are unable to react to hypoxic stimuli by properly activating the hypoxia-inducible factor-1 (HIF-1) pathway, a defect that is further enhanced in the event of a concomitant genotoxic stress. Furthermore, we show that CSB expression is under the control of HIF-1 and has...
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PMID: 18784753
PDF is available here.
Yoichi Y Maekawa,
Yoshiaki Y Minato,
Chieko C Ishifune,
Takeshi T Kurihara,
Akiko A Kitamura,
Hidefumi H Kojima,
Hideo H Yagita,
Mamiko M Sakata-Yanagimoto,
Toshiki T Saito,
Ichiro I Taniuchi,
Shigeru S Chiba,
Saburo S Sone and
Koji K Yasutomo
Abstract
We show here that Notch2-deficient T cells had impaired differentiation into cytotoxic T lymphocytes. In addition, dendritic cells with lower expression of the Notch ligand Delta-like 1 induced the differentiation of cytotoxic T lymphocytes less efficiently. We found that the intracellular domain of...
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PMID: 18724371
PDF is available here.
Abstract
We present evidence that under hypoxia-mimicking conditions p53 acetylation is reduced to a greater extent at K320 site targeted by P300/CBP-associated factor (PCAF) than at K382 site targeted by p300/CBP. The limited amounts of acetylated p53 at K320 are preferentially recruited to the promoter of...
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PMID: 18574470
PDF is available here.
Abstract
We first identified p300 as a specific lysine acetyltransferase, and extracellular-signal-related kinase 2 (Erk2) as a specific kinase for threonine phosphorylation, of RIP140 in vivo. We further determined two specific acetylated lysine residues (Lys(158)/Lys(287)) and phosphorylated threonine resi...
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PMID: 18655826
PDF is available here.
Abstract
These results are consistent with an authentic coactivator function of Zac1's C(2)H(2) zinc finger DNA-binding domain and suggest coactivation by sequence-specific transcription factors as a new facet of transcriptional control....
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PMID: 18663001
PDF is available here.
Abstract
We previously identified a set of transcription regulators, referred to as TIPs (tension-induced/inhibited proteins), with a role in myogenic versus adipogenic differentiation. Here we report that the TIP family comprises eight isoforms, all bearing a SANT (switching-defective protein 3, adaptor 2,...
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PMID: 18710950
PDF is available here.
Abstract
We show by affinity chromatography, protein-protein interaction assays, and biochemical fractionation of nuclear extracts that the histone acetyltransferase (HAT) PCAF associates with actin and hnRNP U. PCAF and the nuclear actin-associated HAT activity detected in the DNase I-bound protein fraction...
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PMID: 18710935
PDF is available here.
Abstract
We find that the acidic domain of MDM2 is necessary to inhibit p300-mediated acetylation of p53 as well as to mediate the deacetylation of p53. Our results indicate that acidic domain of MDM2 provides essential information for acetyltransferase p300 and deacetylase HDAC1 and is indispensable for MDM...
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PMID: 18638452
PDF is available here.
Abstract
We demonstrate that collagen gene expression was markedly elevated in mouse embryonic fibroblasts (MEFs) lacking PPAR-gamma compared to heterozygous control MEFs. Treatment with the PPAR-gamma ligand 15d-PGJ(2) failed to down-regulate collagen gene expression in PPAR-gamma null MEFs, whereas reconst...
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PMID: 18627765
PDF is available here.