Control of histone modifications

Davie, James R.; Spencer, Virginia A.

doi:10.1002/(sici)1097-4644(1999)75:32+<141::aid-jcb17>3.0.co;2-a

Cited by 122 publications

(71 citation statements)

References 40 publications

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“…The acetylation of core histone tails is a dynamic process maintained by histone acetyltransferases (HAT) and histone deacetylases (HDAC). HDACs form complexes with transcriptional corepressors and are believed to repress transcription by removing the acetyl groups from the N-terminal tails of the core histones of chromatin [33]. Our data show that quercetin activated histone deacetylase enzyme activity, which reduced acetylation of histone H3.…”

Section: Discussionmentioning

confidence: 69%

Quercetin augments TRAIL-induced apoptotic death: Involvement of the ERK signal transduction pathway

Kim

Lee

Jeong

et al. 2008

Biochemical Pharmacology

158

115

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Combined treatment with quercetin and TRAIL induced cytotoxicity and enhanced annexin V staining and poly (ADP-ribose) polymerase (PARP) cleavage in human prostate cancer cell lines DU-145 and PC-3. These indicators of apoptosis resulted from the activation of caspase-8, -9, and -3. Although the expression levels of FLIPs, cIAP1, cIAP2, and the Bcl-2 family were not changed in quercetin-treated cells, significant downregulation of survivin occurred. Knockdown survivin by siRNA significantly increased TRAIL-induced apoptosis. We hypothesized that quercetin-induced activation of MAPK (ERK, p38, JNK) is responsible for downregulation of survivin gene expression. To test this hypothesis, we selectively inhibited MAPK during treatment with quercetin. Our data demonstrated that inhibitor of ERK (PD98059), but not p38 MAPK (SB203580) or JNK (SP600125), significantly maintained the intracellular level of survivin during treatment with quercetin. Interestingly, PD98059 also prevented quercetin-induced deacetylation of histone H3. Data from survivin promoter activity assay suggest that the Sp1 transcription factor binds to the survivin promoter region and quercetin inhibits its binding activity through deacetylation of histone H3. Quercetin-induced activation of the ERK-MSK1 signal transduction pathway may be responsible for deacetylation of histone H3. Taken together, our findings suggest that quercetin enhances TRAIL induced apoptosis by inhibition of survivin expression, through ERK-MSK1-mediated deacetylation of H3.

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Section: Discussionmentioning

confidence: 69%

Quercetin augments TRAIL-induced apoptotic death: Involvement of the ERK signal transduction pathway

Kim

Lee

Jeong

et al. 2008

Biochemical Pharmacology

158

115

View full text Add to dashboard Cite

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“…5, A and B). The acetylation of N-terminal tails of histones is correlated with disruption of higher order chromatin structure and activation of transcription, whereas its deacetylation relates to its reversal and repression of transcription (46). Among the histone acetyltransferases that catalyze acetylation of histones, p300/CBP is well established for its role in the regulation of plethora of genes, including cell cycle regulators (47).…”

Section: Discussionmentioning

confidence: 99%

c-ETS1 Facilitates G1/S-phase Transition by Up-regulating Cyclin E and CDK2 Genes and Cooperates with Hepatitis B Virus X Protein for Their Deregulation

Singh¹,

Swarnalatha²,

Kumar

2011

Journal of Biological Chemistry

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Recent studies on the molecular mechanisms responsible for cell cycle deregulation in cancer have puzzled out the role of oncogenes in mediating unscheduled cellular proliferation. This is reminiscence of their activity as proto-oncogenes that drives scheduled cell cycle progression under physiological conditions. Working on the cell cycle regulatory activity of protooncogene, we observed that c-ETS1 transcriptionally up-regulated both cyclin E and CDK2 genes, the master regulators of G 1 /S-phase transition. The process was mediated by kinetic coherence of c-ETS1 expression and its recruitment to both promoters during G 1 /S-phase transition. Furthermore, enforced expression of c-ETS1 helped G 0 -arrested cells to progress into G 1 /S-phases apparently due to the activation of cyclin E/CDK2 genes. Physiological induction of c-ETS1 by EGF showed the remodeling of mononucleosomes bound to the c-ETS1 binding site on both promoters during their activation. The exchange of HDAC1 with histone acetyltransferase-p300 was contemporaneous to the chromatin remodeling with consequent increase in histone H3K9 acetylation. Furthermore, the ATP-dependent chromatin remodeler hBRM1 recruitment was also associated with nucleosome remodeling and promoter occupancy of phospho-Ser5 RNA polymerase II. Intriguingly, the activity of the HBx viral oncoprotein was dependent on c-ETS1 in a hepatotropic manner, which led to the activation of cyclin E/CDK2 genes. Thus, cyclin E and CDK2 genes are key physiological effectors of the c-ETS1 proto-oncogene. Furthermore, c-ETS1 is indispensable for the hepatotropic action of HBx in cell cycle deregulation.

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“…5D) and supercoiled naked DNAs with reduced affinity relative to nucleosomal arrays suggests that both nu- cleosomal DNA and structured domain(s) of the histone octamer may mediate interactions with HAT A2. Several Gcn5p-containing HAT A complexes have been isolated to date, including HAT A2, ADA, and SAGA (8,9,34,35). Our compositional analyses and substrate specificity data suggest that HAT A2 may be the "core" enzymatic complex for this family of histone acetyltransferases.…”

Section: Discussionmentioning

confidence: 99%

The Yeast Histone Acetyltransferase A2 Complex, but Not Free Gcn5p, Binds Stably to Nucleosomal Arrays

Sendra

Tse

Hansen

2000

Journal of Biological Chemistry

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We have investigated the structural basis for the differential catalytic function of the yeast Gcn5p-containing histone acetyltransferase (HAT) A2 complex and free recombinant yeast Gcn5p (rGcn5p). HAT A2 is shown to be a unique complex that contains Gcn5p, Ada2p, and Ada3p, but not proteins specific to other related HAT A complexes, e.g. ADA, SAGA. Nevertheless, HAT A2 produces the same unique polyacetylation pattern of nucleosomal substrates reported previously for ADA and SAGA, demonstrating that proteins specific to the ADA and SAGA complexes do not influence the enzymatic activity of Gcn5p within the HAT A2 complex. To investigate the role of substrate interactions in the differential behavior of free and complexed Gcn5p, sucrose density gradient centrifugation was used to characterize the binding of HAT A2 and free rGcn5p to intact and trypsinized nucleosomal arrays, H3/H4 tetramer arrays, and nucleosome core particles. We find that HAT A2 forms stable complexes with all nucleosomal substrates tested. In distinct contrast, rGcn5p does not interact stably with nucleosomal arrays, despite being able to specifically monoacetylate the H3 N terminus of nucleosomal substrates. Our data suggest that the ability of the HAT A2 complex to bind stably to nucleosomal arrays is functionally related to both local and global acetylation by the complexed and free forms of Gcn5p.Histone acetylation is a dynamic process in vivo involving multiple acetyltransferase and deacetylase enzymes (1-3). Acetylation occurs at specific lysine residues of each of the core histone N termini, and influences chromatin structure and function at all levels from the folded chromatin fiber to the nucleosome (4 -6). Because of the key role of acetylation in transcription and replication, a great deal of attention has been focused on the properties and functions of recently identified histone acetyltransferase enzymes (HATs).1 HAT A enzymes (e.g. Gcn5p, Esa1p) primarily are involved in transcriptional regulation, whereas HAT B enzymes (e.g. Hat1p) are thought to participate in replication coupled-chromatin assembly. The Tetrahymena equivalent of yeast Gcn5p (Gcn5p) was the first specific HAT A enzyme to be cloned and overexpressed (7), and the Gcn5 family of HATs remains the focus of intense investigation (see Refs. 5,8,and 9, and references therein).The catalytic function of yeast Gcn5p in vitro is strongly dependent on whether the enzyme is free or is a component of large multiprotein complexes such as HAT A2, ADA, and SAGA (8, 9). Purified ADA and SAGA complexes both have been shown to contain the non-DNA-binding, transcriptional adaptor proteins Ada2p and Ada3p (8 -10). Consistent with these in vitro results, genetic experiments in yeast have documented that mutations in Ada2p or Ada3p yield phenotypes identical to loss of Gcn5p in terms of both transcriptional regulation at specific gene loci (11, 12) and cell growth (11, 13). In addition, several specific proteins have recently been identified as unique components of ADA or SAGA. For exam...

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Control of histone modifications

Cited by 122 publications

References 40 publications

Quercetin augments TRAIL-induced apoptotic death: Involvement of the ERK signal transduction pathway

Quercetin augments TRAIL-induced apoptotic death: Involvement of the ERK signal transduction pathway

c-ETS1 Facilitates G1/S-phase Transition by Up-regulating Cyclin E and CDK2 Genes and Cooperates with Hepatitis B Virus X Protein for Their Deregulation

The Yeast Histone Acetyltransferase A2 Complex, but Not Free Gcn5p, Binds Stably to Nucleosomal Arrays

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