Epigenetic effects of dietary butyrate on hepatic histone acetylation and enzymes of biotransformation in chicken

2013 ◽  
Vol 61 (4) ◽  
pp. 477-490 ◽  
Author(s):  
Gábor Mátis ◽  
Zsuzsanna Neogrády ◽  
György Csikó ◽  
Péter Gálfi ◽  
Hedvig Fébel ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Broiler Chickens ◽  
Cell Function ◽  
Enzyme Assays ◽  
Histone H2a ◽  
Epigenetic Effects ◽  
Acetylation State ◽  
Core Histones ◽  
Microsomal Cytochrome P450

The aim of the study was to investigate the in vivo epigenetic influences of dietary butyrate supplementation on the acetylation state of core histones and the activity of drug-metabolising microsomal cytochrome P450 (CYP) enzymes in the liver of broiler chickens in the starter period. One-day-old Ross 308 broilers were fed a starter diet without or with sodium butyrate (1.5 g/kg feed) for 21 days. After slaughtering, nucleus and microsome fractions were isolated from the exsanguinated liver by multi-step differential centrifugation. Histone acetylation level was detected from hepatocyte nuclei by Western blotting, while microsomal CYP activity was examined by specific enzyme assays. Hyperacetylation of hepatic histone H2A at lysine 5 was observed after butyrate supplementation, providing modifications in the epigenetic regulation of cell function. No significant changes could be found in the acetylation state of the other core histones at the acetylation sites examined. Furthermore, butyrate did not cause any changes in the drugmetabolising activity of hepatic microsomal CYP2H and CYP3A37 enzymes, which are mainly involved in the biotransformation of most xenobiotics in chicken. These data indicate that supplementation of the diet with butyrate probably does not have any pharmacokinetic interactions with simultaneously applied xenobiotics.

scholarly journals Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression

2000 ◽  
Vol 14 (7) ◽  
pp. 804-816 ◽  
Author(s):  
Yasuhiko Takahashi ◽  
Joseph B. Rayman ◽  
Brian David Dynlacht
Keyword(s):  
Histone Acetylation ◽  
Cell Cycle Progression ◽  
Control Cell ◽  
Gene Activation ◽  
Mammalian Cell Cycle ◽  
E2f Transcription Factor ◽  
Acetylation State ◽  
Core Histones ◽  
Related Proteins

The E2F transcription factor plays a pivotal role in the timely activation of gene expression during mammalian cell cycle progression, whereas pRB and related proteins control cell growth in part through the ability to block the action of E2F. To identify physiologically important E2F-responsive promoters and to study their occupancy and histone acetylation state in vivo, we have taken advantage of a cross-linking approach in synchronized, living cells. We find that the pattern of E2F and pRB-related polypeptides recruited to these promoters changes in a strikingly dynamic fashion as cells progress from quiescence into G1 and S phase: Repression of each promoter in quiescent cells is associated with recruitment of E2F-4 and p130 and low levels of histone acetylation, but by late G1, these proteins are replaced largely by E2F-1 and E2F-3, in concert with acetylation of histones H3 and H4 and gene activation. These findings suggest that repression and activation of E2F-responsive genes may occur through distinct E2F heterodimers that direct the sequential recruitment of enzymes able to deacetylate and then acetylate core histones.

scholarly journals The Nuclear Actin-related Protein of Saccharomyces cerevisiae, Act3p/Arp4, Interacts with Core Histones

1999 ◽  
Vol 10 (8) ◽  
pp. 2595-2605 ◽  
Author(s):  
Masahiko Harata ◽  
Yukako Oma ◽  
Shigeki Mizuno ◽  
Yi Wei Jiang ◽  
David J. Stillman ◽  
...  
Keyword(s):  
Nuclear Actin ◽  
Histone H2a ◽  
Related Protein ◽  
The Core ◽  
Core Histones ◽  
Episomal Dna ◽  
Two Hybrid ◽  
Far Western Blot ◽  
Correct Expression

Act3p/Arp4, an essential actin-related protein ofSaccharomyces cerevisiae located within the nucleus, is, according to genetic data, involved in transcriptional regulation. In addition to the basal core structure of the actin family members, which is responsible for ATPase activity, Act3p possesses two insertions, insertions I and II, the latter of which is predicted to form a loop-like structure protruding from beyond the surface of the molecule. Because Act3p is a constituent of chromatin but itself does not bind to DNA, we hypothesized that insertion II might be responsible for an Act3p-specific function through its interaction with some other chromatin protein. Far Western blot and two-hybrid analyses revealed the ability of insertion II to bind to each of the core histones, although with somewhat different affinities. Together with our finding of coimmunoprecipitation of Act3p with histone H2A, this suggests the in vivo existence of a protein complex required for correct expression of particular genes. We also show that a conditionalact3 mutation affects chromatin structure of an episomal DNA molecule, indicating that the putative Act3p complex may be involved in the establishment, remodeling, or maintenance of chromatin structures.

Kinetic analysis of histone acetylation turnover and Trichostatin A induced hyper- and hypoacetylation in alfalfa

2002 ◽  
Vol 80 (3) ◽  
pp. 279-293 ◽  
Author(s):  
Jakob H Waterborg ◽  
Tamás Kapros
Keyword(s):  
Gene Expression ◽  
Steady State ◽  
Histone Acetylation ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Similar Rate ◽  
Lysine Methylation ◽  
Histone H2a ◽  
Turnover Rates

Dynamic histone acetylation is a characteristic of chromatin transcription. The first estimates for the rate of acetylation turnover of plants are reported, measured in alfalfa cells by pulse, pulse-chase, and steady-state acetylation labeling. Acetylation turnover half-lives of about 0.5 h were observed by all methods used for histones H3, H4, and H2B. This is consistent with the rate at which changes in gene expression occur in plants. Treatment with histone deacetylase inhibitor Trichostatin A (TSA) induced hyperacetylation at a similar rate. Replacement histone variant H3.2, preferentially localized in highly acetylated chromatin, displayed faster acetyl turnover. Histone H2A with a low level of acetylation was not subject to rapid turnover or hyperacetylation. Patterns of acetate labeling revealed fundamental differences between histone H3 versus histones H4 and H2B. In H3, acetylation of all molecules, limited by lysine methylation, had similar rates, independent of the level of lysine acetylation. Acetylation of histones H4 and H2B was seen in only a fraction of all molecules and involved multiacetylation. Acetylation turnover rates increased from mono- to penta- and hexaacetylated forms, respectively. TSA was an effective inhibitor of alfalfa histone deacetylases in vivo and caused a doubling in steady-state acetylation levels by 4–6 h after addition. However, hyperacetylation was transient due to loss of TSA inhibition. TSA-induced overexpression of cellular deacetylase activity produced hypoacetylation by 18 h treatment with enhanced acetate turnover labeling of alfalfa histones. Thus, application of TSA to change gene expression in vivo in plants may have unexpected consequences.

Dynamics of histone acetylation in vivo. A function for acetylation turnover?

2002 ◽  
Vol 80 (3) ◽  
pp. 363-378 ◽  
Author(s):  
Jakob H Waterborg
Keyword(s):  
Histone Acetylation ◽  
Gene Transcription ◽  
Turnover Rates ◽  
Nucleosome Remodeling ◽  
Amino Terminal ◽  
Rapid Changes ◽  
Core Histones ◽  
Reversible Modification ◽  
Amino Terminal Domain

Histone acetylation, discovered more than 40 years ago, is a reversible modification of lysines within the amino-terminal domain of core histones. Amino-terminal histone domains contribute to the compaction of genes into repressed chromatin fibers. It is thought that their acetylation causes localized relaxation of chromatin as a necessary but not sufficient condition for processes that repackage DNA such as transcription, replication, repair, recombination, and sperm formation. While increased histone acetylation enhances gene transcription and loss of acetylation represses and silences genes, the function of the rapid continuous or repetitive acetylation and deacetylation reactions with half-lives of just a few minutes remains unknown. Thirty years of in vivo measurements of acetylation turnover and rates of change in histone modification levels have been reviewed to identify common chromatin characteristics measured by distinct protocols. It has now become possible to look across a wider spectrum of organisms than ever before and identify common features. The rapid turnover rates in transcriptionally active and competent chromatin are one such feature. While ubiquitously observed, we still do not know whether turnover itself is linked to chromatin transcription beyond its contribution to rapid changes towards hyper- or hypoacetylation of nucleosomes. However, recent experiments suggest that turnover may be linked directly to steps in gene transcription, interacting with nucleosome remodeling complexes.Key words: histone, acetylation, turnover, chromatin, transcription.

scholarly journals Nuclear Import of Histone H2a and H2b Is Mediated by a Network of Karyopherins

2001 ◽  
Vol 153 (2) ◽  
pp. 251-262 ◽  
Author(s):  
Nima Mosammaparast ◽  
Kelley R. Jackson ◽  
Yurong Guo ◽  
Cynthia J. Brame ◽  
Jeffrey Shabanowitz ◽  
...  
Keyword(s):  
Nuclear Import ◽  
Fluorescent Protein ◽  
Nuclear Localization Sequence ◽  
Temperature Sensitive ◽  
Histone H2a ◽  
Amino Terminal ◽  
Core Histones ◽  
Localization Sequence ◽  
Green Fluorescent

The first step in the assembly of new chromatin is the cell cycle–regulated synthesis and nuclear import of core histones. The core histones include H2A and H2B, which are assembled into nucleosomes as heterodimers. We show here that the import of histone H2A and H2B is mediated by several members of the karyopherin (Kap; importin) family. An abundant complex of H2A, H2B, and Kap114p was detected in cytosol. In addition, two other Kaps, Kap121p and Kap123p, and the histone chaperone Nap1p were isolated with H2A and H2B. Nap1p is not necessary for the formation of the Kap114p-H2A/H2B complex or for import of H2A and H2B. We demonstrate that both histones contain a nuclear localization sequence (NLS) in the amino-terminal tail. Fusions of the NLSs to green fluorescent protein were specifically mislocalized to the cytoplasm in kap mutant strains. In addition, we detected a specific mislocalization in a kap95 temperature-sensitive strain, suggesting that this Kap is also involved in the import of H2A and H2B in vivo. Importantly, we show that Kap114p, Kap121p, and Kap95 interact directly with both histone NLSs and that RanGTP inhibits this association. These data suggest that the import of H2A and H2B is mediated by a network of Kaps, in which Kap114p may play the major role.

scholarly journals Micronuclei and the cytoplasm of growing Tetrahymena contain a histone acetylase activity which is highly specific for free histone H4.

1988 ◽  
Vol 106 (4) ◽  
pp. 1017-1026 ◽  
Author(s):  
R Richman ◽  
L G Chicoine ◽  
M P Collini ◽  
R G Cook ◽  
C D Allis
Keyword(s):  
Thermal Inactivation ◽  
Specific Activity ◽  
Enzyme Assays ◽  
Histone H4 ◽  
Core Histones ◽  
Cytosolic Extract ◽  
Histone Acetyltransferase Activity

Salt extracts prepared from purified micronuclei and the cytoplasm of growing Tetrahymena contain a histone acetylase (also referred to as histone acetyltransferase) activity which is highly specific for H4 when tested as a free histone. With both extracts, H4 is acetylated first at position 4 (monoacetylated) or positions 4 and 11 (diacetylated), sites diagnostic of deposition-related acetylation of newly synthesized H4 in vivo. As the concentration of cytosolic extract is decreased in the in vitro reactions, acetylation of H3 is also observed. Neither activity acetylates histone in a chromatin form. These activities are distinct from a macronuclear acetylase which acetylates H3 and H4 (macro- or micronuclear) equally well as free histones and which acetylates all four core histones when mononucleosomes are used as substrate. As well, the micronuclear and cytoplasmic activities give similar thermal-inactivation profiles which are different from that of the macronuclear activity. In situ enzyme assays demonstrate a macronuclear-specific activity which acetylates endogenous macronuclear chromatin and an independent micronuclear-cytosolic activity which is able to act upon exogenously added free H4. These results argue strongly that an identical acetylase is responsible for the micronuclear and cytoplasmic activity which is either modified or altogether distinct from that in macronuclei.

Untargeted tail acetylation of histones in chromatin: lessons from yeastThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB’s 51st Annual Meeting – Epigenetics and Chromatin Dynamics, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 87 (1) ◽  
pp. 107-116 ◽  
Author(s):  
R. Magnus N. Friis ◽  
Michael C. Schultz
Keyword(s):  
Histone Acetylation ◽  
Peer Review Process ◽  
State Level ◽  
Chromatin Dynamics ◽  
Amino Terminal ◽  
Lysine Residues ◽  
Acetylation State ◽  
Core Histones ◽  
Functional Consequences ◽  
Chromatin Acetylation

Dynamic acetylation of lysine residues in the amino-terminal tails of the core histones is functionally important for the regulation of diverse DNA-dependent processes in the nucleus, including replication, transcription, and DNA repair. The targeted and untargeted activities of histone lysine acetylases (KATs) and deacetylases (HDACs) both contribute to the dynamics of chromatin acetylation. While the mechanisms and functional consequences of targeted on histone acetylation are well understood, relatively little is known about untargeted histone acetylation. Here, we review the current understanding of the mechanisms by which untargeted KAT and HDAC activities modulate the acetylation state of nucleosomal histones, focusing on results obtained for H3 and H4 in budding yeast. We also highlight unresolved problems in this area, including the question of how a particular steady-state level of untargeted acetylation is set in the absence of cis-dependent mechanisms that instruct the activity of KATs and HDACs.

scholarly journals p300-Mediated acetylation facilitates the transfer of histone H2A–H2B dimers from nucleosomes to a histone chaperone

2000 ◽  
Vol 14 (15) ◽  
pp. 1899-1907 ◽  
Author(s):  
Takashi Ito ◽  
Tsuyoshi Ikehara ◽  
Takeya Nakagawa ◽  
W. Lee Kraus ◽  
Masami Muramatsu
Keyword(s):  
Histone Acetylation ◽  
Chromatin Remodeling ◽  
Transcriptional Activator ◽  
Histone Chaperone ◽  
Assembly System ◽  
Transcriptional Activators ◽  
Histone H2a ◽  
Nucleosome Structure ◽  
Core Histones ◽  
Chromatin Remodeling Complexes

We have used a purified recombinant chromatin assembly system, including ACF (Acf-1 + ISWI) and NAP-1, to examine the role of histone acetylation in ATP-dependent chromatin remodeling. The binding of a transcriptional activator (Gal4–VP16) to chromatin assembled using this recombinant assembly system dramatically enhances the acetylation of nucleosomal core histones by the histone acetyltransferase p300. This effect requires both the presence of Gal4-binding sites in the template and the VP16-activation domain. Order-of-addition experiments indicate that prior activator-meditated, ATP-dependent chromatin remodeling by ACF is required for the acetylation of nucleosomal histones by p300. Thus, chromatin remodeling, which requires a transcriptional activator, ACF and ATP, is an early step in the transcriptional process that regulates subsequent core histone acetylation. Glycerol gradient sedimentation and immunoprecipitation assays demonstrate that the acetylation of histones by p300 facilitates the transfer of H2A–H2B from nucleosomes to NAP-1. The results from these biochemical experiments suggest that (1) transcriptional activators (e.g., Gal4–VP16) and chromatin remodeling complexes (e.g., ACF) induce chromatin remodeling in the absence of histone acetylation; (2) transcriptional activators recruit histone acetyltransferases (e.g., p300) to promoters after chromatin remodeling has occurred; and (3) histone acetylation is important for a step subsequent to chromatin remodeling and results in the transfer of histone H2A–H2B dimers from nucleosomes to a histone chaperone such as NAP-1. Our results indicate a precise role for histone acetylation, namely to alter the structure of nucleosomes (e.g., facilitate the loss of H2A–H2B dimers) that have been remodeled previously by the action of ATP-dependent chromatin remodeling complexes. Thus, transcription from chromatin templates is ordered and sequential, with precise timing and roles for ATP-dependent chromatin remodeling, subsequent histone acetylation, and alterations in nucleosome structure.

scholarly journals The histone H2A deubiquitinase Usp16 regulates hematopoiesis and hematopoietic stem cell function

2015 ◽  
Vol 113 (1) ◽  
pp. E51-E60 ◽  
Author(s):  
Yue Gu ◽  
Amanda E. Jones ◽  
Wei Yang ◽  
Shanrun Liu ◽  
Qian Dai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Ubiquitin Ligase ◽  
Cell Function ◽  
Lymphoid Organ ◽  
Histone H2a ◽  
Hematopoietic Stem

Epigenetic mechanisms play important regulatory roles in hematopoiesis and hematopoietic stem cell (HSC) function. Subunits of polycomb repressive complex 1 (PRC1), the major histone H2A ubiquitin ligase, are critical for both normal and pathological hematopoiesis; however, it is unclear which of the several counteracting H2A deubiquitinases functions along with PRC1 to control H2A ubiquitination (ubH2A) level and regulates hematopoiesis in vivo. Here we investigated the function of Usp16 in mouse hematopoiesis. Conditional deletion of Usp16 in bone marrow resulted in a significant increase of global ubH2A level and lethality. Usp16 deletion did not change HSC number but was associated with a dramatic reduction of mature and progenitor cell populations, revealing a role in governing HSC lineage commitment. ChIP- and RNA-sequencing studies in HSC and progenitor cells revealed that Usp16 bound to many important hematopoietic regulators and that Usp16 deletion altered the expression of genes in transcription/chromosome organization, immune response, hematopoietic/lymphoid organ development, and myeloid/leukocyte differentiation. The altered gene expression was partly rescued by knockdown of PRC1 subunits, suggesting that Usp16 and PRC1 counterbalance each other to regulate cellular ubH2A level and gene expression in the hematopoietic system. We further discovered that knocking down Cdkn1a (p21cip1), a Usp16 target and regulated gene, rescued the altered cell cycle profile and differentiation defect of Usp16-deleted HSCs. Collectively, these studies identified Usp16 as one of the histone H2A deubiquitinases, which coordinates with the H2A ubiquitin ligase PRC1 to regulate hematopoiesis, and revealed cell cycle regulation by Usp16 as key for HSC differentiation.

scholarly journals A single histone acetyltransferase from Tetrahymena macronuclei catalyzes deposition-related acetylation of free histones and transcription-related acetylation of nucleosomal histones.

1987 ◽  
Vol 105 (1) ◽  
pp. 127-135 ◽  
Author(s):  
L G Chicoine ◽  
R Richman ◽  
R G Cook ◽  
M A Gorovsky ◽  
C D Allis
Keyword(s):  
Enzyme Activity ◽  
Histone Acetylation ◽  
Histone Acetyltransferase ◽  
Histone H3 ◽  
Heat Inactivation ◽  
Histone H4 ◽  
Isolated Nuclei ◽  
Core Histones ◽  
Histone Acetyltransferase Activity

A salt-extracted histone acetyltransferase activity from Tetrahymena macronuclei acetylates mostly histone H3 and H4 when free histones are used as substrate. Free histone H4 is acetylated first at position 11 (monoacetylated) or positions 11 and 4 (diacetylated). This activity strongly resembles in vivo, deposition-related acetylation of newly synthesized histones. When acetylase-free mononucleosomes are used as substrate, all four core histones are acetylated by the same extract, and H4 is acetylated first at position 7 (monoacetylated) or positions 7 and 4 (diacetylated). In this respect, the activity of the extract is indistinguishable from postsynthetic, transcription-related histone acetylation that occurs in vivo or in isolated nuclei. Heat inactivation curves with both substrates are indistinguishable, and free histones compete with chromatin for limiting amounts of enzyme activity. These results argue strongly that two distinct, biologically important histone acetylations, one deposition related and one transcription related, are carried out by a single acetyltransferase.

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