Gcn5- and Elp3-induced histone H3 acetylation regulates hsp70 gene transcription in yeast

2008 ◽  
Vol 409 (3) ◽  
pp. 779-788 ◽  
Author(s):  
Qiuju Han ◽  
Jun Lu ◽  
Jizhou Duan ◽  
Dongmei Su ◽  
Xiaozhe Hou ◽  
...  
Keyword(s):  
Heat Shock ◽  
Histone Acetylation ◽  
Rna Polymerase Ii ◽  
Gene Transcription ◽  
Transcriptional Activation ◽  
Histone H3 ◽  
Hsp70 Gene ◽  
Transcriptional Initiation ◽  
Hsp Genes ◽  
H3 Acetylation

The purpose of this study was to elucidate the mechanisms by which histone acetylation participates in transcriptional regulation of hsp70 (heat-shock protein 70) genes SSA3 and SSA4 in yeast. Our results indicated that histone acetylation was required for the transcriptional activation of SSA3 and SSA4. The HATs (histone acetyltransferases) Gcn5 (general control non-derepressible 5) and Elp3 (elongation protein 3) modulated hsp70 gene transcription by affecting the acetylation status of histone H3. Although the two HATs possessed overlapping function regarding the acetylation of histone H3, they affected hsp70 gene transcription in different ways. The recruitment of Gcn5 was Swi/Snf-dependent and was required for HSF (heat-shock factor) binding and affected RNAPII (RNA polymerase II) recruitment, whereas Elp3 exerted its roles mainly through affecting RNAPII elongation. These results provide insights into the effects of Gcn5 and Elp3 in hsp70 gene transcription and underscore the importance of histone acetylation for transcriptional initiation and elongation in hsp genes.

scholarly journals PfGCN5-Mediated Histone H3 Acetylation Plays a Key Role in Gene Expression in Plasmodium falciparum

2007 ◽  
Vol 6 (7) ◽  
pp. 1219-1227 ◽  
Author(s):  
Long Cui ◽  
Jun Miao ◽  
Tetsuya Furuya ◽  
Xinyi Li ◽  
Xin-zhuan Su ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Histone Acetylation ◽  
Transcriptional Activation ◽  
Histone H3 ◽  
Epigenetic Mechanism ◽  
Promoter Regions ◽  
Specific Expression ◽  
Transcriptional Initiation ◽  
Translational Start

ABSTRACT Histone acetylation, regulated by the opposing actions of histone acetyltransferases (HATs) and deacetylases, is an important epigenetic mechanism in eukaryotic transcription. Although an acetyltransferase (PfGCN5) has been shown to preferentially acetylate histone H3 at K9 and K14 in Plasmodium falciparum, the scale of histone acetylation in the parasite genome and its role in transcriptional activation are essentially unknown. Using chromatin immunoprecipitation (ChIP) and DNA microarray, we mapped the global distribution of PfGCN5, histone H3K9 acetylation (H3K9ac) and trimethylation (H3K9m3) in the P. falciparum genome. While the chromosomal distributions of H3K9ac and PfGCN5 were similar, they are radically different from that of H3K9m3. In addition, there was a positive, though weak correlation between relative occupancy of H3K9ac on individual genes and the levels of gene expression, which was inversely proportional to the distance of array elements from the putative translational start codons. In contrast, H3K9m3 was negatively correlated with gene expression. Furthermore, detailed mapping of H3K9ac for selected genes using ChIP and real-time PCR in three erythrocytic stages detected stage-specific peak H3K9ac enrichment at the putative transcriptional initiation sites, corresponding to stage-specific expression of these genes. These data are consistent with H3K9ac and H3K9m3 as epigenetic markers of active and silent genes, respectively. We also showed that treatment with a PfGCN5 inhibitor led to reduced promoter H3K9ac and gene expression. Collectively, these results suggest that PfGCN5 is recruited to the promoter regions of genes to mediate histone acetylation and activate gene expression in P. falciparum.

scholarly journals Signal Transduction Pathways Leading to Heat Shock Transcription

2010 ◽  
Vol 2 ◽  
pp. STI.S3994 ◽  
Author(s):  
S. K. Calderwood ◽  
Y. Wang ◽  
X. Xie ◽  
M. A Khaleque ◽  
S. D Chou ◽  
...  
Keyword(s):  
Heat Shock ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Feedback Inhibition ◽  
Open Reading Frames ◽  
Transcriptional Level ◽  
Transcriptional Initiation ◽  
Nucleosome Remodeling ◽  
Shock Proteins ◽  
Hsp Genes

Heat shock proteins (HSP) are essential for intracellular protein folding during stress and protect cells from denaturation and aggregation cascades that can lead to cell death. HSP genes are regulated at the transcriptional level by heat shock transcription factor 1 (HSF1) that is activated by stress and binds to heat shock elements in HSP genes. The activation of HSF1 during heat shock involves conversion from an inert monomer to a DNA binding trimer through a series of intramolecular folding rearrangements. However, the trigger for HSF1 at the molecular level is unclear and hypotheses for this process include reversal of feedback inhibition of HSF1 by molecular chaperones and heat-induced binding to large non-coding RNAs. Heat shock also causes a profound modulation in cell signaling pathways that lead to protein kinase activation and phosphorylation of HSF1 at a number of regulatory serine residues. HSP genes themselves exist in an accessible chromatin conformation already bound to RNA polymerase II. The RNA polymerase II is paused on HSP promoters after transcribing a short RNA sequence proximal to the promoter. Activation by heat shock involves HSF1 binding to the promoter and release of the paused RNA polymerase II followed by further rounds of transcriptional initiation and elongation. HSF1 is thus involved in both initiation and elongation of HSP RNA transcripts. Recent studies indicate important roles for histone modifications on HSP genes during heat shock. Histone modification occurs rapidly after stress and may be involved in promoting nucleosome remodeling on HSP promoters and in the open reading frames of HSP genes. Understanding these processes may be key to evaluating mechanisms of deregulated HSP expression that plays a key role in neurodegeneration and cancer.

scholarly journals Involvement of histone acetyltransferase (HAT) in ethanol-induced acetylation of histone H3 in hepatocytes: potential mechanism for gene expression

2005 ◽  
Vol 289 (6) ◽  
pp. G1124-G1136 ◽  
Author(s):  
Pil-Hoon Park ◽  
Robert W. Lim ◽  
Shivendra D. Shukla
Keyword(s):  
Gene Expression ◽  
Histone Acetylation ◽  
Transcriptional Activation ◽  
Specific Activity ◽  
Histone H3 ◽  
Ethanol Treatment ◽  
H3 Acetylation ◽  
I Gene

Ethanol treatment increases gene expression in the liver through mechanisms that are not clearly understood. Histone acetylation has been shown to induce transcriptional activation. We have investigated the characteristics and mechanisms of ethanol-induced histone H3 acetylation in rat hepatocytes. Immunocytochemical and immunoblot analysis revealed that ethanol treatment significantly increased H3 acetylation at Lys9 with negligible effects at Lys14, -18, and -23. Acute in vivo administration of alcohol in rats produced the same results as in vitro observations. Nuclear extracts from ethanol-treated hepatocytes increased acetylation in H3 peptide to a greater extent than extracts from untreated cells, suggesting that ethanol either increased the expression level or the specific activity of histone acetyltransferases (HAT). Use of different H3 peptides indicated that ethanol selectively modulated HAT(s) targeting H3-Lys9. Treatment with acetate, an ethanol metabolite, also increased acetylation of H3-Lys9 and modulated HAT(s) in the same manner as ethanol, suggesting that acetate mediates the ethanol-induced effect on HAT. Inhibitors of MEK (U0126) and JNK (SP600125), but not p38 MAPK inhibitor (SB203580), suppressed ethanol-induced H3 acetylation. However, U0126 and SP600125 did not significantly affect ethanol-induced effect on HAT, suggesting that ERK and JNK regulate histone acetylation through a separate pathway(s) that does not involve modulation of HAT. Chromatin immunoprecipitation assay demonstrated that ethanol treatment increased the association of the class I alcohol dehydrogenase (ADH I) gene with acetylated H3-Lys9. These data provide first evidence that ethanol increases acetylation of H3-Lys9 through modulation of HAT(s) and that histone acetylation may underlie the mechanism for ethanol-induced ADH I gene expression.

Coordinate changes in heat shock element-binding activity and HSP70 gene transcription rates in human cells

1988 ◽  
Vol 8 (11) ◽  
pp. 4736-4744
Author(s):  
D D Mosser ◽  
N G Theodorakis ◽  
R I Morimoto
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Heat Shock ◽  
Gene Transcription ◽  
Elevated Temperatures ◽  
Binding Activity ◽  
Heat Shock Gene ◽  
Hsp70 Gene ◽  
Heat Shock Element ◽  
Amino Acid Analogs

Activation of human heat shock gene transcription by heat shock, heavy metal ions, and amino acid analogs required the heat shock element (HSE) in the HSP70 promoter. Both heat shock- and metal ion-induced HSP70 gene transcription occurred independently of protein synthesis, whereas induction by amino acid analogs required protein synthesis. We identified a HSE-binding activity from control cells which was easily distinguished by a gel mobility shift assay from the stress-induced HSE-binding activity which appeared following heat shock or chemically induced stress. The kinetics of HSP70 gene transcription paralleled the rapid appearance of stress-induced HSE-binding activity. During recovery from heat shock, both the rate of HSP70 gene transcription and stress-induced HSE-binding activity levels declined and the control HSE-binding activity reappeared. The DNA contacts of the control and stress-induced HSE-binding activities deduced by methylation interference were similar but not identical. While stable complexes with HSE were formed with extracts from both control and stressed cells in vitro at 25 degrees C, only the stress-induced complex was detected when binding reactions were performed at elevated temperatures.

scholarly journals Promoter-specific changes in initiation, elongation and homeostasis of histone H3 acetylation during CBP/p300 inhibition

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Emily Hsu ◽  
Nathan R Zemke ◽  
Arnold J Berk
Keyword(s):  
Rna Polymerase Ii ◽  
Control Point ◽  
Histone H3 ◽  
Airway Epithelial Cells ◽  
Proximal Region ◽  
Transferase Activity ◽  
Transcriptional Elongation ◽  
Elongation Complex ◽  
Histone H3 Acetylation ◽  
H3 Acetylation

Regulation of RNA Polymerase II (Pol2) elongation in the promoter proximal region is an important and ubiquitous control point for gene expression in metazoans. We report that transcription of the adenovirus 5 E4 region is regulated during the release of paused Pol2 into productive elongation by recruitment of the super elongation complex (SEC), dependent on promoter H3K18/27 acetylation by CBP/p300. We also establish that this is a general transcriptional regulatory mechanism that applies to ~6% of expressed protein-coding genes in primary human airway epithelial cells. We observed that a homeostatic mechanism maintains promoter, but not enhancer H3K18/27ac in response to extensive inhibition of CBP/p300 acetyl transferase activity by the highly specific small molecule inhibitor A-485. Further, our results suggest a function for BRD4 association at enhancers in regulating paused Pol2 release at nearby promoters. Taken together, our results uncover processes regulating transcriptional elongation by promoter region histone H3 acetylation and homeostatic maintenance of promoter, but not enhancer, H3K18/27ac in response to inhibition of CBP/p300 acetyl transferase activity.

Co-dependent recruitment of Ino80p and Snf2p is required for yeast CUP1 activation

2014 ◽  
Vol 92 (1) ◽  
pp. 69-75 ◽  
Author(s):  
Roshini N. Wimalarathna ◽  
Po Yun Pan ◽  
Chang-Hui Shen
Keyword(s):  
Rna Polymerase ◽  
Histone Acetylation ◽  
Rna Polymerase Ii ◽  
Chromatin Remodeling ◽  
Transcriptional Activation ◽  
Copper Toxicity ◽  
Yeast Cells ◽  
Chromatin Remodelers ◽  
Insight Into ◽  
Cup1 Promoter

In yeast, Ace1p-dependent induction of CUP1 is responsible for protecting cells from copper toxicity. Although the mechanism of yeast CUP1 induction has been studied intensively, it is still uncertain which chromatin remodelers are involved in CUP1 transcriptional activation. Here, we show that yeast cells are inviable in the presence of copper when either chromatin remodeler, Ino80p or Snf2p, is not present. This inviability is due to the lack of CUP1 expression in ino80Δ and snf2Δ cells. Subsequently, we observe that both Ino80p and Snf2p are present at the promoter and they are responsible for recruiting chromatin remodeling activity to the CUP1 promoter under induced conditions. These results suggest that they directly participate in CUP1 transcriptional activation. Furthermore, the codependent recruitment of both INO80 and SWI/SNF depends on the presence of the transcriptional activator, Ace1p. We also demonstrate that both remodelers are required to recruit RNA polymerase II and targeted histone acetylation, indicating that remodelers are recruited to the CUP1 promoter before RNA polymerase II and histone acetylases. These observations provide evidence for the mechanism of CUP1 induction. As such, we propose a model that describes novel insight into the order of events in CUP1 activation.

Regulation of HSP70 by PTH: a model of gene regulation not mediated by changes in cAMP levels

1996 ◽  
Vol 271 (1) ◽  
pp. C121-C129 ◽  
Author(s):  
S. Fukayama ◽  
B. Lanske ◽  
J. Guo ◽  
H. M. Kronenberg ◽  
F. R. Bringhurst
Keyword(s):  
Heat Shock ◽  
Adenylate Cyclase ◽  
Gene Transcription ◽  
Cellular Response ◽  
Host Cells ◽  
Osteoblastic Cell ◽  
Target Cells ◽  
Hsp70 Gene ◽  
Hsp70 Mrna ◽  
Human Hsp70

Parathyroid hormone (PTH) activates both adenylate cyclase and phospholipase C in target cells, and cloned PTH/PTH-related protein (PTHrP) receptor can mediate both responses when expressed in host cells such as LLC-PK1 renal epithelial cells. Because calcitonin (CT) is known to augment 70-kDa heat shock protein (HSP70) mRNA by an adenosine 3',5'-cyclic monophosphate (cAMP)-independent mechanism in LLC-PK1 cells, we examined regulation of HSP70 transcription by PTH in these cells. Like CT, human PTH-(1-34) [hPTH-(1-34); 10(-10) to 10(-7) M)] increased porcine HSP70 mRNA and human HSP70 promoter-chloramphenicol acetyltransferase (CAT) expression within 4 h in LLC-PK1 cells that stably express > or = 100,000 PTH/PTHrP receptors per cell. The effect of PTH on HSP70 mRNA was not mimicked by cAMP analogues, forskolin, phorbol esters, Ca2+ ionophores, or alpha-thrombin; was insensitive to pertussis toxin; and was not due to increased mRNA stability. The upregulation of HSP70 gene transcription by hPTH (and CT) was clearly observed even after deletion of the functional heat shock consensus element in the promoter region of the human HSP70/CAT reporter. Upregulation of HSP70 transcription via endogenous PTH receptors also was observed in the osteoblastic cell lines SaOS-2 and ROS 17/2.8. Regulation of HSP70 gene transcription by PTH may be a common cellular response to the hormone, which, in some cells, may not be mediated by activation of adenylate cyclase or protein kinase C.

Differential histone acetylation in the Amygdala leads to fear memory consolidation and extinction

2015 ◽  
Vol 1 (1) ◽  
Author(s):  
Vandana Ranjan ◽  
Sanjay Singh ◽  
Sarfraj Ahmad Siddiqui ◽  
M Y Khan ◽  
Anand Prakash
Keyword(s):  
Histone Acetylation ◽  
Memory Consolidation ◽  
Histone H3 ◽  
Fear Memory ◽  
Memory Formation ◽  
Acetylation Level ◽  
Creb Activation ◽  
Conditioning Model ◽  
Histone H3 Acetylation ◽  
H3 Acetylation

<p>In the present study, a fear-conditioning model in rats was used to gauge the changes in the histone acetylation level in the<br />different nuclei of amygdala during fear memory consolidation and its extinction. It was found by immunohistochemical<br />examination of Amygdala that during the fear memory consolidation histone H3 acetylation level was significantly<br />increased in the Central amygdala (CeA), the output of the fear circuitry, as compared to the unconditioned group and<br />subsequently, when this fear memory was extinguished during fear extinction, the histone H3 acetylation levels decreased<br />significantly as compared to the conditioned group. However, in another nuclei of the amygdala, the intercalated cells<br />(ITCs) the Acetyl H3 levels increased during extinction and but not in the conditioned group as compared to the<br />unconditioned group. The p-ERK and p-CREB levels also significantly varied in the different nuclei of amygdala<br />between the two groups and showed correlation with the Histone acetylation changes observed in these groups. In<br />conclusion the present study points out that the memory formation, during fear memory consolidation and its extinction,<br />may be dependent on differential neuronal activity under epigenetic control through acetylation at k-9 residue of histone<br />H3, in different regions of the amygdala as evident by the p-ERK and p-CREB activation, which are the markers for<br />activity of neurons and memory formation.</p>

scholarly journals Rapid changes in Drosophila transcription after an instantaneous heat shock.

1993 ◽  
Vol 13 (6) ◽  
pp. 3456-3463 ◽  
Author(s):  
T O'Brien ◽  
J T Lis
Keyword(s):  
Heat Shock ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Uv Light ◽  
Hsp70 Gene ◽  
Rapid Induction ◽  
Rapid Changes ◽  
Rapid Activation ◽  
Kinetics Of

Heat shock rapidly activates expression of some genes and represses others. The kinetics of changes in RNA polymerase distribution on heat shock-modulated genes provides a framework for evaluating the mechanisms of activation and repression of transcription. Here, using two methods, we examined the changes in RNA polymerase II association on a set of Drosophila genes at 30-s intervals following an instantaneous heat shock. In the first method, Drosophila Schneider line 2 cells were quickly frozen to halt transcription, and polymerase distribution was analyzed by a nuclear run-on assay. RNA polymerase transcription at the 5' end of the hsp70 gene could be detected within 30 to 60 s of induction, and by 120 s the first wave of polymerase could already be detected near the 3' end of the gene. A similar rapid induction was found for the small heat shock genes (hsp22, hsp23, hsp26, and hsp27). In contrast to this rapid activation, transcription of the histone H1 gene was found to be rapidly repressed, with transcription reduced by approximately 90% within 300 s of heat shock. Similar results were obtained by an in vivo UV cross-linking assay. In this second method, cell samples removed at 30-s intervals were irradiated with 40-microseconds bursts of UV light from a Xenon flash lamp, and the distribution of polymerase was examined by precipitating UV cross-linked protein-DNA complexes with an antibody to RNA polymerase II. Both approaches also showed the in vivo rate of movement of the first wave of RNA polymerase through the hsp70 gene to be approximately 1.2 kb/min.

scholarly journals Aryl Hydrocarbon Receptor-Mediated Transcription: Ligand-Dependent Recruitment of Estrogen Receptor α to 2,3,7,8-Tetrachlorodibenzo- p-Dioxin-Responsive Promoters

2005 ◽  
Vol 25 (13) ◽  
pp. 5317-5328 ◽  
Author(s):  
Jason Matthews ◽  
Björn Wihlén ◽  
Jane Thomsen ◽  
Jan-Åke Gustafsson
Keyword(s):  
Estrogen Receptor ◽  
Aryl Hydrocarbon Receptor ◽  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Time Course ◽  
Estrogen Receptor Α ◽  
Time Dependent ◽  
Promoter Regions ◽  
Aryl Hydrocarbon ◽  
H3 Acetylation

ABSTRACT Using chromatin immunoprecipitation assays, we studied the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated recruitment of the aryl hydrocarbon receptor (AhR) and several coregulators to the CYP1A1 promoter. AhR displayed a time-dependent recruitment, reaching a peak at 75 min and maintaining promoter occupancy for the remainder of the time course. Recruitment of AhR was followed by TIF2/SRC2, which preceded CBP, histone H3 acetylation, and RNA polymerase II (RNAPII). Simultaneous recruitment to the enhancer and the TATA box region suggests the formation of a large multiprotein complex bridging the two promoter regions. Interestingly, estrogen receptor α (ERα) displayed a TCDD- and time-dependent recruitment to the CYP1A1 promoter, which was increased by cotreatment with estradiol. Transfection in HuH7 human liver cells confirmed previously reported ERα enhancement of AhR activity. In contrast, TCDD did not induce the recruitment of ERα to the estrogen-responsive pS2 promoter, and after 120 min of cotreatment with estradiol, ERα is still present on the CYP1A1 promoter but no longer at pS2. RNA interference studies with T47D cells support a role for ERα in TCDD-dependent CYP1A1 expression. Our data suggest that ERα acts as a coregulator of AhR-mediated transcriptional activation and that the recruitment of ERα by AhR represents a novel mechanism AhR-ERα cross talk.

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