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.

Epigenetic Regulation of Spinal CXCR2 Signaling in Incisional Hypersensitivity in Mice

2013 ◽  
Vol 119 (5) ◽  
pp. 1198-1208 ◽  
Author(s):  
Yuan Sun ◽  
Peyman Sahbaie ◽  
De-Yong Liang ◽  
Wen-Wu Li ◽  
Xiang-Qi Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Acetylation ◽  
Hydroxamic Acid ◽  
Regulation Of Gene Expression ◽  
Histone H3 ◽  
Anacardic Acid ◽  
Epigenetic Mechanism ◽  
Suberoylanilide Hydroxamic Acid ◽  
Promoter Regions ◽  
Hyperalgesic Priming

Abstract Background: The regulation of gene expression in nociceptive pathways contributes to the induction and maintenance of pain sensitization. Histone acetylation is a key epigenetic mechanism controlling chromatin structure and gene expression. Chemokine CC motif receptor 2 (CXCR2) is a proinflammatory receptor implicated in neuropathic and inflammatory pain and is known to be regulated by histone acetylation in some settings. The authors sought to investigate the role of histone acetylation on spinal CXCR2 signaling after incision. Methods: Groups of 5–8 mice underwent hind paw incision. Suberoylanilide hydroxamic acid and anacardic acid were used to inhibit histone deacetylase and histone acetyltransferase, respectively. Behavioral measures of thermal and mechanical sensitization as well as hyperalgesic priming were used. Both message RNA quantification and chromatin immunoprecipitation analysis were used to study the regulation of CXCR2 and ligand expression. Finally, the selective CXCR2 antagonist SB225002 was administered intrathecally to reveal the function of spinal CXCR2 receptors after hind paw incision. Results: Suberoylanilide hydroxamic acid significantly exacerbated mechanical sensitization after incision. Conversely, anacardic acid reduced incisional sensitization and also attenuated incision-induced hyperalgesic priming. Overall, acetylated histone H3 at lysine 9 was increased in spinal cord tissues after incision, and enhanced association of acetylated histone H3 at lysine 9 with the promoter regions of CXCR2 and keratinocyte-derived chemokine (CXCL1) was observed as well. Blocking CXCR2 reversed mechanical hypersensitivity after hind paw incision. Conclusions: Histone modification is an important epigenetic mechanism regulating incision-induced nociceptive sensitization. The spinal CXCR2 signaling pathway is one epigenetically regulated pathway controlling early and latent sensitization after incision.

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 Histone acetylation orchestrates wound-induced transcriptional activation and cellular reprogramming in Arabidopsis

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Bart Rymen ◽  
Ayako Kawamura ◽  
Alice Lambolez ◽  
Soichi Inagaki ◽  
Arika Takebayashi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Acetylation ◽  
Transcriptional Activation ◽  
Temporal Dynamics ◽  
Callus Formation ◽  
Early Time ◽  
Cellular Reprogramming ◽  
Epigenetic Mechanism ◽  
Transcriptional Responses ◽  
Physiological Processes

Abstract Plant somatic cells reprogram and regenerate new tissues or organs when they are severely damaged. These physiological processes are associated with dynamic transcriptional responses but how chromatin-based regulation contributes to wound-induced gene expression changes and subsequent cellular reprogramming remains unknown. In this study we investigate the temporal dynamics of the histone modifications H3K9/14ac, H3K27ac, H3K4me3, H3K27me3, and H3K36me3, and analyze their correlation with gene expression at early time points after wounding. We show that a majority of the few thousand genes rapidly induced by wounding are marked with H3K9/14ac and H3K27ac before and/or shortly after wounding, and these include key wound-inducible reprogramming genes such as WIND1, ERF113/RAP2.6 L and LBD16. Our data further demonstrate that inhibition of GNAT-MYST-mediated histone acetylation strongly blocks wound-induced transcriptional activation as well as callus formation at wound sites. This study thus uncovered a key epigenetic mechanism that underlies wound-induced cellular reprogramming in plants.

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.

scholarly journals Global Histone H3 Lysine 4 Trimethylation (H3K4me3) Landscape Changes in Response to TGFβ

2021 ◽  
Vol 14 ◽  
pp. 251686572110517
Author(s):  
Ankit Naik ◽  
Nidhi Dalpatraj ◽  
Noopur Thakur
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Expression Patterns ◽  
Histone H3 ◽  
Epigenetic Mechanism ◽  
Stable Gene ◽  
Regulation Of Transcription ◽  
Functional Categories ◽  
Positive Regulation ◽  
Histone H4 Acetylation

TGFβ expression acts as a biomarker of poor prognosis in prostate cancer. It plays a dual functional role in prostate cancer. In the early stages of the tumor, it acts as a tumor suppressor while at the later stages of tumor development, it promotes metastasis. The molecular mechanisms of action of TGFβ are largely understood through the canonical and non-canonical signal transduction pathways. Our understanding of the mechanisms that establish transient TGFβ stimulation into stable gene expression patterns remains incomplete. Epigenetic marks like histone H3 modifications are directly linked with gene expression and they play an important role in tumorigenesis. In this report, we performed chromatin immunoprecipitation-sequencing (ChIP-Seq) to identify the genome-wide regions that undergo changes in histone H3 Lysine 4 trimethylation (H3K4me3) occupancy in response to TGFβ stimulation. We also show that TGFβ stimulation can induce acute epigenetic changes through the modulation of H3K4me3 signals at genes belonging to special functional categories in prostate cancer. TGFβ induces the H3K4me3 on its own ligands like TGFβ, GDF1, INHBB, GDF3, GDF6, BMP5 suggesting a positive feedback loop. The majority of genes were found to be involved in the positive regulation of transcription from the RNA polymerase II promoter in response to TGFβ. Other functional categories were intracellular protein transport, brain development, EMT, angiogenesis, antigen processing, antigen presentation via MHC class II, lipid transport, embryo development, histone H4 acetylation, positive regulation of cell cycle arrest, and genes involved in mitotic G2 DNA damage checkpoints. Our results link TGFβ stimulation to acute changes in gene expression through an epigenetic mechanism. These findings have broader implications on epigenetic bases of acute gene expression changes caused by growth factor stimulation.

scholarly journals Genome-Wide Relationships between TAF1 and Histone Acetyltransferases in Saccharomyces cerevisiae

2006 ◽  
Vol 26 (7) ◽  
pp. 2791-2802 ◽  
Author(s):  
Melissa Durant ◽  
B. Franklin Pugh
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Histone Acetylation ◽  
Rna Polymerase Ii ◽  
Histone Acetyltransferases ◽  
Histone H4 ◽  
Promoter Regions ◽  
Genome Wide ◽  
Acetylated Histone H4

ABSTRACT Histone acetylation regulates gene expression, yet the functional contributions of the numerous histone acetyltransferases (HATs) to gene expression and their relationships with each other remain largely unexplored. The central role of the putative HAT-containing TAF1 subunit of TFIID in gene expression raises the fundamental question as to what extent, if any, TAF1 contributes to acetylation in vivo and to what extent it is redundant with other HATs. Our findings herein do not support the basic tenet that TAF1 is a major HAT in Saccharomyces cerevisiae, nor do we find that TAF1 is functionally redundant with other HATs, including Gcn5, Elp3, Hat1, Hpa2, Sas3, and Esa1, which is in contrast to previous conclusions regarding Gcn5. Our findings do reveal that of these HATs, only Gcn5 and Esa1 contribute substantially to gene expression genome wide. Interestingly, histone acetylation at promoter regions throughout the genome does not require TAF1 or RNA polymerase II, indicating that most acetylation is likely to precede transcription and not depend upon it. TAF1 function has been linked to Bdf1, which binds TFIID and acetylated histone H4 tails, but no linkage between TAF1 and the H4 HAT Esa1 has been established. Here, we present evidence for such a linkage through Bdf1.

scholarly journals Drosophila Ada2b Is Required for Viability and Normal Histone H3 Acetylation

2004 ◽  
Vol 24 (18) ◽  
pp. 8080-8089 ◽  
Author(s):  
Dai Qi ◽  
Jan Larsson ◽  
Mattias Mannervik
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Protein Complexes ◽  
P53 Protein ◽  
Polytene Chromosomes ◽  
Histone H3 ◽  
Saga Complex ◽  
Histone H3 Acetylation ◽  
H3 Acetylation

ABSTRACT Regulation of chromatin through histone acetylation is an important step in gene expression. The Gcn5 histone acetyltransferase is part of protein complexes, e.g., the SAGA complex, that interact with transcriptional activators, targeting the enzyme to specific promoters and assisting in recruitment of the basal RNA polymerase transcription machinery. The Ada2 protein directly binds to Gcn5 and stimulates its catalytic activity. Drosophila contains two Ada2 proteins, Drosophila Ada2a (dAda2a) and dAda2b. We have generated flies that lack dAda2b, which is part of a Drosophila SAGA-like complex. dAda2b is required for viability in Drosophila, and its deletion causes a reduction in histone H3 acetylation. A global hypoacetylation of chromatin was detected on polytene chromosomes in dAda2b mutants. This indicates that the dGcn5-dAda2b complex could have functions in addition to assisting in transcriptional activation through gene-specific acetylation. Although the Drosophila p53 protein was previously shown to interact with the SAGA-like complex in vitro, we find that p53 induction of reaper gene expression occurs normally in dAda2b mutants. Moreover, dAda2b mutant animals show excessive p53-dependent apoptosis in response to gamma radiation. Based on this result, we speculate that dAda2b may be necessary for efficient DNA repair or generation of a DNA damage signal. This could be an evolutionarily conserved function, since a yeast ada2 mutant is also sensitive to a genotoxic agent.

scholarly journals 134INCOMPLETE HISTONE ACETYLATION OF SOMATIC CHROMATIN IN BOVINE OOCYTES

2004 ◽  
Vol 16 (2) ◽  
pp. 189
Author(s):  
G. Wee ◽  
S.-H. Kim ◽  
K.P. Kim ◽  
S. Yeo ◽  
D.-B. Koo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Somatic Cell ◽  
Histone Acetylation ◽  
Transcriptional Activation ◽  
Linear Models ◽  
Trichostatin A ◽  
Specific Inhibitor ◽  
Early Embryo ◽  
Image Analyzer ◽  
Cell Nuclei

Histone acetylation as an important regulatory mechanism of chromatin structure preceeding zygotic gene expression in early embryo development. After fertilization, transcriptional activation of the embryo begins during the S/G2 phase of the first cell cycle. However, the precise mechanism underlying activation of zygotic transcription remains to be understood, especially in bovine nuclear transfer (NT) embryos. It is known that acetylation of histone H4 lysine 5 (H4K5) represents hyperacetylation state, which is correlated with gene expression. In this study, the acetylation of H4K5 was observed during pronuclear formation by using immunofluorescence analysis with anti-AcH4K5. Our data were analyzed by the general linear models (GLM) procedure of the SAS. In IVF embryos, acetylation of H4K5 occurred on the paternal chromatin at 8h after fertilization but did not occur on the maternal chromatin until 10h after fertilization. Reconstructed oocytes with deactylated somatic cell nuclei began to show signs of acetylation on chromatin at 3h after fusion. When acetylation intensity was calculated using an image analyzer, IVF embryos presented a higher acetylation signal than NT embryos (P<0.05). To induce hyperacetylation in NT embryos, somatic cells were exposed to trichostatin A (TSA, 1μM for 60h), a specific inhibitor of histone deacetylase (HDAC), prior to NT. Acetylated signals of H4K5 increased significantly in TSA-treated cells as compared with non-treated cells (P<0.05). The reconstructed embryos with TSA-treated cells showed a higher fluorescence intensity than the oocytes with non-treated cells (P<0.05), but weak signals compared to IVF embryos. Thus, the results demonstrated low histone acetylation level of somatic cell nuclei after NT during the zygotic progress. Our findings suggest that developmental failures of NT embryos may be due to incomplete chromatin remodeling of somatic cell nuclei during early embryonic development.

CpG islands in genes showing tissue-specific expression

1990 ◽  
Vol 326 (1235) ◽  
pp. 207-215 ◽  
Keyword(s):  
Gene Expression ◽  
Cpg Islands ◽  
Housekeeping Genes ◽  
Tissue Expression ◽  
Proximal Promoter ◽  
Cell Type ◽  
Promoter Regions ◽  
Specific Expression ◽  
Tissue Specific ◽  
Single Cell Type

Patterns of DNA methylation at GpG dinucleotides and their relations with gene expression are complex. Methylation-free CpG clusters, so-called HTF islands, are most often associated with the promoter regions of housekeeping genes, whereas genes expressed in a single-cell type are usually deficient in these sequences. However, in the human carbonic anhydrase (CA) gene family, both the ubiquitously expressed CAII and the muscle specific CAIII appear to have such CpG islands although erythrocyte-specific CAI does not. The CAII island is quantitatively more CpG rich than that of CAIII, with a CpG :GpC ratio of 0.94 compared with 0.82 for CAIII. Estimation of CpG:GpC ratios in the proximal-promoter regions of 44 vertebrate genes suggest that 40% of genes with tissue-specific or limited tissue distribution may show methylation-free CpG clusters in their promoter regions. In many cases the CpG:GpC ratio is less than that found in housekeeping genes and this may reflect variation in the interaction of CpG clusters with regulatory factors that define different patterns of tissue expression.

scholarly journals Single-Cell Analysis Reveals Distinct Gene Expression and Heterogeneity in Male and FemalePlasmodium falciparumGametocytes

mSphere ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Katelyn A. Walzer ◽  
Danielle M. Kubicki ◽  
Xiaohu Tang ◽  
Jen-Tsan Ashley Chi
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Single Cell ◽  
Specific Expression ◽  
Male And Female ◽  
Content Type ◽  
Population Analyses ◽  
Specific Differentiation ◽  
Female Specific ◽  
Gender Specific

ABSTRACTSexual reproduction is an obligate step in thePlasmodium falciparumlife cycle, with mature gametocytes being the only form of the parasite capable of human-to-mosquito transmission. Development of male and female gametocytes takes 9 to 12 days, and although more than 300 genes are thought to be specific to gametocytes, only a few have been postulated to be male or female specific. Because these genes are often expressed during late gametocyte stages and for some, male- or female-specific transcript expression is debated, the separation of male and female populations is technically challenging. To overcome these challenges, we have developed an unbiased single-cell approach to determine which transcripts are expressed in male versus female gametocytes. Using microfluidic technology, we isolated single mid- to late-stage gametocytes to compare the expression of 91 genes, including 87 gametocyte-specific genes, in 90 cells. Such analysis identified distinct gene clusters whose expression was associated with male, female, or all gametocytes. In addition, a small number of male gametocytes clustered separately from female gametocytes based on sex-specific expression independent of stage. Many female-enriched genes also exhibited stage-specific expression. RNA fluorescentin situhybridization of male and female markers validated the mutually exclusive expression pattern of male and female transcripts in gametocytes. These analyses uncovered novel male and female markers that are expressed as early as stage III gametocytogenesis, providing further insight intoPlasmodiumsex-specific differentiation previously masked in population analyses. Our single-cell approach reveals the most robust markers for sex-specific differentiation inPlasmodiumgametocytes. Such single-cell expression assays can be generalized to all eukaryotic pathogens.IMPORTANCEMost human deaths that result from malaria are caused by the eukaryotic parasitePlasmodium falciparum. The only form of this parasite that is transmitted to the mosquito is the sexual form, called the gametocyte. The production of mature gametocytes can take up to 2 weeks and results in phenotypically distinct males and females, although what causes this gender-specific differentiation remains largely unknown. Here, we demonstrate the first use of microfluidic technology to capture single gametocytes and determine their temporal sex-specific gene expression in an unbiased manner. We were able to determine male or female identity of single cells based on the upregulation of gender-specific genes as early as mid-stage gametocytes. This analysis has revealed strong markers for male and female gametocyte differentiation that were previously concealed in population analyses. Similar single-cell analyses in eukaryotic pathogens using this method may uncover rare cell types and heterogeneity previously masked in population studies.

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