scholarly journals The majority of histone acetylation is a consequence of transcription

2019 ◽  
Author(s):  
Benjamin J.E. Martin ◽  
Julie Brind’Amour ◽  
Kristoffer N. Jensen ◽  
Anastasia Kuzmin ◽  
Zhen Cheng Liu ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Chromatin Immunoprecipitation ◽  
Transcriptional Activity ◽  
Immunoblot Analysis ◽  
Histone Acetyltransferases ◽  
Histone H4 ◽  
Transcription Inhibition ◽  
Histone H4 Acetylation ◽  
Chromatin Immunoprecipitation Sequencing

AbstractHistone acetylation is a ubiquitous hallmark of transcriptional activity, but whether the link is of a causal or consequential nature is still a matter of debate. In this study we resolve this question. Using both immunoblot analysis and chromatin immunoprecipitation-sequencing (ChIP-seq) in S. cerevisiae, we show that the majority of histone acetylation is dependent on transcription. Loss of histone H4 acetylation upon transcription inhibition is partially explained by depletion of histone acetyltransferases (HATs) from gene bodies, implicating transcription in HAT targeting. Despite this, HAT occupancy alone poorly predicts histone acetylation, suggesting that HAT activity is regulated at a step post-recruitment. Collectively, these data show that the majority of histone acetylation is a consequence of RNAPII promoting both the recruitment and activity of histone acetyltransferases.

scholarly journals Histone Acetylation at Promoters Is Differentially Affected by Specific Activators and Repressors

2001 ◽  
Vol 21 (8) ◽  
pp. 2726-2735 ◽  
Author(s):  
Jutta Deckert ◽  
Kevin Struhl
Keyword(s):  
Histone Acetylation ◽  
Transcriptional Activation ◽  
Transcriptional Activity ◽  
Histone H4 ◽  
Dramatic Decrease ◽  
Histone H4 Acetylation ◽  
Apparent Decrease ◽  
H3 Acetylation ◽  
The Relationship ◽  
Target Promoters

ABSTRACT We analyzed the relationship between histone acetylation and transcriptional regulation at 40 Saccharomyces cerevisiaepromoters that respond to specific activators and repressors. In accord with the general correlation between histone acetylation and transcriptional activity, Gcn4 and the general stress activators (Msn2 and Msn4) cause increased acetylation of histones H3 and H4. Surprisingly, Gal4-dependent activation is associated with a dramatic decrease in histone H4 acetylation, whereas acetylation of histone H3 is unaffected. A specific decrease in H4 acetylation is also observed, to a lesser extent, at promoters activated by Hap4, Adr1, Met4, and Ace1. Activation by heat shock factor has multiple effects; H4 acetylation increases at some promoters, whereas other promoters show an apparent decrease in H3 and H4 acetylation that probably reflects nucleosome loss or gross alteration of chromatin structure. Repression by targeted recruitment of the Sin3-Rpd3 histone deacetylase is associated with decreased H3 and H4 acetylation, whereas repression by Cyc8-Tup1 is associated with decreased H3 acetylation but variable effects on H4 acetylation; this suggests that Cyc8-Tup1 uses multiple mechanisms to reduce histone acetylation at promoters. Thus, individual activators confer distinct patterns of histone acetylation on target promoters, and transcriptional activation is not necessarily associated with increased acetylation. We speculate that the activator-specific decrease in histone H4 acetylation is due to blocking the access or function of an H4-specific histone acetylase such as Esa1.

scholarly journals The Tor Pathway Regulates Gene Expression by Linking Nutrient Sensing to Histone Acetylation

2003 ◽  
Vol 23 (2) ◽  
pp. 629-635 ◽  
Author(s):  
John R. Rohde ◽  
Maria E. Cardenas
Keyword(s):  
Gene Expression ◽  
Cell Growth ◽  
Histone Acetylation ◽  
Nutrient Sensing ◽  
Gene Promoters ◽  
Histone H4 ◽  
Tor Pathway ◽  
Histone H4 Acetylation ◽  
Promoter Occupancy ◽  
Histone H4 Deacetylation

ABSTRACT The Tor pathway mediates cell growth in response to nutrient availability, in part by inducing ribosomal protein (RP) gene expression via an unknown mechanism. Expression of RP genes coincides with recruitment of the Esa1 histone acetylase to RP gene promoters. We show that inhibition of Tor with rapamycin releases Esa1 from RP gene promoters and leads to histone H4 deacetylation without affecting promoter occupancy by Rap1 and Abf1. Genetic and biochemical evidence identifies Rpd3 as the major histone deacetylase responsible for reversing histone H4 acetylation at RP gene promoters in response to Tor inhibition by rapamycin or nutrient limitation. Our results illustrate that the Tor pathway links nutrient sensing with histone acetylation to control RP gene expression and cell growth.

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 Glucocorticoid Receptor Recruitment of Histone Deacetylase 2 Inhibits Interleukin-1β-Induced Histone H4 Acetylation on Lysines 8 and 12

2000 ◽  
Vol 20 (18) ◽  
pp. 6891-6903 ◽  
Author(s):  
Kazuhiro Ito ◽  
Peter J. Barnes ◽  
Ian M. Adcock
Keyword(s):  
Gene Expression ◽  
Histone Acetylation ◽  
Histone Deacetylase ◽  
Interleukin 1Β ◽  
Dependent Manner ◽  
Histone H4 ◽  
Altered Expression ◽  
Gm Csf ◽  
Low Concentrations ◽  
Histone H4 Acetylation

ABSTRACT We have investigated the ability of dexamethasone to regulate interleukin-1β (IL-1β)-induced gene expression, histone acetyltransferase (HAT) and histone deacetylase (HDAC) activity. Low concentrations of dexamethasone (10−10 M) repress IL-1β-stimulated granulocyte-macrophage colony-stimulating factor (GM-CSF) expression and fail to stimulate secretory leukocyte proteinase inhibitor expression. Dexamethasone (10−7 M) and IL-1β (1 ng/ml) both stimulated HAT activity but showed a different pattern of histone H4 acetylation. Dexamethasone targeted lysines K5 and K16, whereas IL-1β targeted K8 and K12. Low concentrations of dexamethasone (10−10 M), which do not transactivate, repressed IL-1β-stimulated K8 and K12 acetylation. Using chromatin immunoprecipitation assays, we show that dexamethasone inhibits IL-1β-enhanced acetylated K8-associated GM-CSF promoter enrichment in a concentration-dependent manner. Neither IL-1β nor dexamethasone elicited any GM-CSF promoter association at acetylated K5 residues. Furthermore, we show that GR acts both as a direct inhibitor of CREB binding protein (CBP)-associated HAT activity and also by recruiting HDAC2 to the p65-CBP HAT complex. This action does not involve de novo synthesis of HDAC protein or altered expression of CBP or p300/CBP-associated factor. This mechanism for glucocorticoid repression is novel and establishes that inhibition of histone acetylation is an additional level of control of inflammatory gene expression. This further suggests that pharmacological manipulation of of specific histone acetylation status is a potentially useful approach for the treatment of inflammatory diseases.

scholarly journals NuA4 Subunit Yng2 Function in Intra-S-Phase DNA Damage Response

2002 ◽  
Vol 22 (23) ◽  
pp. 8215-8225 ◽  
Author(s):  
John S. Choy ◽  
Stephen J. Kron
Keyword(s):  
Dna Damage ◽  
Dna Replication ◽  
Histone Acetylation ◽  
Trichostatin A ◽  
S Phase ◽  
Open Chromatin ◽  
Histone H4 ◽  
Histone H4 Acetylation ◽  
Histone Deacetylase Inhibitor Trichostatin ◽  
Nucleosomal Histone

ABSTRACT While regulated transcription requires acetylation of histone N-terminal tails to promote an open chromatin conformation, a similar role for histone acetylation in DNA replication and/or repair remains to be established. Cells lacking the NuA4 subunit Yng2 are viable but critically deficient for genome-wide nucleosomal histone H4 acetylation. We found that yng2 mutants are specifically sensitized to DNA damage in S phase induced by cdc8 or cdc9 mutations, hydroxyurea, camptothecin, or methylmethane sulfonate (MMS). In yng2, MMS treatment causes a persistent Mec1-dependent intra-S-phase checkpoint delay characterized by slow DNA repair. Restoring H4 acetylation with the histone deacetylase inhibitor trichostatin A promotes checkpoint recovery. In turn, mutants lacking the histone H3-specific acetyltransferase GCN5 are similarly sensitive to intra-S-phase DNA damage. The inviability of gcn5 yng2 double mutants suggests overlapping roles for H3 and H4 acetylation in DNA replication and repair. Paradoxically, haploid yng2 mutants do not tolerate mutations in genes important for nonhomologous end joining repair yet remain proficient for homologous recombination. Our results implicate nucleosomal histone acetylation in maintaining genomic integrity during chromosomal replication.

scholarly journals Genome-wide dysregulation of histone acetylation in the Parkinson’s disease brain

2019 ◽  
Author(s):  
Lilah Toker ◽  
Gia T Tran ◽  
Janani Sundaresan ◽  
Ole-Bjørn Tysnes ◽  
Guido Alves ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Chromatin Immunoprecipitation ◽  
Genetic Risk ◽  
Neurodegenerative Disorder ◽  
Unknown Etiology ◽  
Transcriptomic Data ◽  
Genome Wide ◽  
A Genome ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Epigenetic Signatures

AbstractParkinson disease (PD) is a complex neurodegenerative disorder of largely unknown etiology. While several genetic risk factors have been identified, the involvement of epigenetics in the pathophysiology of PD is mostly unaccounted for. We conducted a histone acetylome-wide association study in PD, using brain tissue from two independent cohorts of cases and controls. Immunoblotting revealed increased acetylation at several histone sites in PD, with the most prominent change observed for H3K27, a marker of active promoters and enhancers. Chromatin immunoprecipitation sequencing (ChIP-seq) further indicated that H3K27 hyperacetylation in the PD brain is a genome-wide phenomenon, with a strong predilection for genes implicated in the disease, including SNCA, PARK7, PRKN and MAPT. Integration of the ChIP-seq with transcriptomic data revealed that the correlation between promoter H3K27 acetylation and gene expression is attenuated in PD patients, suggesting that H3K27 acetylation may be decoupled from transcription in the PD brain. Our findings strongly suggest that dysregulation of histone acetylation plays an important role in the pathophysiology of PD and identify novel epigenetic signatures associated with the disease.

scholarly journals Stable Isotope Tracing In Vivo Reveals A Metabolic Bridge Linking The Microbiota To Host Histone Acetylation

2021 ◽  
Author(s):  
Peder J Lund ◽  
Leah A Gates ◽  
Marylene Leboeuf ◽  
Sarah A Smith ◽  
Lillian Chau ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Stable Isotope ◽  
Histone Acetylation ◽  
Histone Deacetylases ◽  
Energy Homeostasis ◽  
Acid Oxidation ◽  
Histone H4 ◽  
Isotope Tracing ◽  
Histone H4 Acetylation

The gut microbiota influences host epigenetics by fermenting dietary fiber into butyrate. Although butyrate could promote histone acetylation by inhibiting histone deacetylases, it may also undergo oxidation to acetyl-CoA, a necessary cofactor for histone acetyltransferases. Here, we find that epithelial cells from germ-free mice harbor a loss of histone H4 acetylation across the genome except at promoter regions. Using stable isotope tracing in vivo with 13C-labeled fiber, we demonstrate that the microbiota supplies carbon for histone acetylation. Subsequent metabolomic profiling revealed hundreds of labeled molecules and supported a microbial contribution to host fatty acid metabolism, which declined in response to colitis and correlated with reduced expression of genes involved in fatty acid oxidation. These results illuminate the flow of carbon from the diet to the host via the microbiota, disruptions to which may affect energy homeostasis in the distal gut and contribute to the development of colitis.

scholarly journals Partnership between epigenetic reader BRD4 and transcription factor CEBPD

2020 ◽  
Author(s):  
Qingwei Wang ◽  
Mengxue Zhang ◽  
Go Urabe ◽  
Bowen Wang ◽  
Hatice Gulcin Ozer ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Histone Acetylation ◽  
Chromatin Immunoprecipitation ◽  
State Transition ◽  
Immune Cell ◽  
Neointimal Hyperplasia ◽  
Mrna Levels ◽  
Enhancer Binding Protein ◽  
Chromatin Immunoprecipitation Sequencing

AbstractVascular smooth muscle cell (SMC) state/phenotype transitions underlie neointimal hyperplasia (IH) predisposing to cardiovascular diseases. Bromodomain protein BRD4 is a histone acetylation reader and enhancer mark that co-activates transcription elongation. CCAAT enhancer binding protein delta (CEBPD) is a transcription factor typically studied in adipogenesis and immune cell differentiation. Here we investigated the association between BRD4 and CEBPD in SMC state transition.Chromatin immunoprecipitation sequencing (ChIPseq) showed enrichment of BRD4 and histone acetylation (H3K27ac) at Cebpd and enhancer in rat carotid arteries undergoing IH. In vitro, BRD4 silencing with siRNA reduced SMC expression of CEBPD. Bromodomain-1 but not bromodoamin-2 accounted for this BRD4 function. Endogenous BRD4 co-IP’ed with CEBPD; Cebpd promoter and enhancer DNA fragments co-IP’ed with CEBPD or endogenous BRD4 (ChIP-qPCR). These co-IPs were abolished by the BRD4 bromodomain blocker JQ1. TNFα upregulated both BRD4 and CEBPD. Silencing CEBPD averted TNFα-induced inflammatory SMC state transition (heightened IL-1β, IL6, and MCP-1 mRNA levels), so did JQ1. CEBPD overexpression increased PDGFRα preferentially over PDGFRβ; so did TNFα, and JQ1 abolished TNFα’s effect.Our data reveal a BRD4/CEBPD partnership that promotes CEBPD’s own transcription and inflammatory SMC state transition, thus shedding new light on epigenetic reader and transcription factor cooperative actions in SMC pathobiology.

scholarly journals 73 ABNORMAL REPROGRAMMING OF HISTONE ACETYLATION IN CLONED BOVINE EMBRYOS

2005 ◽  
Vol 17 (2) ◽  
pp. 186
Author(s):  
G. Wee ◽  
D.-B. Koo ◽  
M.-J. Kang ◽  
S.J. Moon ◽  
K.-K. Lee ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Histone Acetylation ◽  
Early Stage ◽  
Somatic Cells ◽  
Epigenetic Reprogramming ◽  
Early Embryonic Development ◽  
Histone H4 ◽  
Normal Cells ◽  
Histone H4 Acetylation ◽  
Late Telophase

Histone acetylation plays an important role in the chromatin structure prior to zygotic gene expression during early embryonic development. Successful animal clones indicate that differentiated somatic nuclei must be reprogrammed to some extent during pre-implantation development. However, the molecular mechanisms regarding epigenetic reprogramming of somatic nuclei in the early-stage embryos are poorly understood. To test this, the patterns of hyperacetylated histone H4 lysine 5 (AcH4K5) in the nuclear-transferred (NT) embryos were monitored, comparing in vitro fertilized (IVF) embryos and Trichostatin A (TSA)-NT embryos with TSA-treated cells. The intensity signals of AcH4K5 were observed in early-stage embryos and somatic cells (bovine ear skin fibroblasts composed of about 80% at G0/G1 stage) by immunofluorescence analysis with anti-AcH4K5 using image the analyzer system, SigmaScan-pro V5.01 (SPSS, Inc., Chicago, IL, USA). Our data were analyzed by analysis of variance (ANOVA) using an SAS package (SAS Institute, Inc., Cary, NC, USA). Somatic cells were exposed to TSA (1 μM for 60 h), a specific inhibitor of histone deacetylase (HDAC), to induce hyperacetylation prior to somatic cell nuclear transfer. Signal intensity for AcH4K5 in TSA-treated cells (n = 80) was significantly increased (P < 0.05), which was approximately double compared to that of normal cells (n = 80). In normal cells, histone H4 acetylation was profoundly reduced from the pro-metaphase to the early telophase and then reappeared at the late telophase. Acetylation signals of TSA-treated cells gradually increased to the early anaphase, abruptly decreased at the late anaphase and the early telophase, and recovered during late telophase. During early embryonic development (1 cell to 8 cell stage), NT embryos (n = 8) were hypoacetylated at the metaphase, whereas IVF (n = 10) and TSA-NT embryos (n = 8) were hyperacetylated. Our findings demonstrate that aberrant epigenetic reprogramming of histone modification occurs as early as the pronuclear stage in cloned embryos.

Sign in / Sign up

Export Citation Format

Share Document