Histone acetyltransferase in chromatin. Evidence for in vitro enzymatic transfer of acetate from acetyl-coenzyme A to histones.
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Acetates↗
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Studies on histones. 5. The histones of the Crocker sarcoma and spontaneous mammary tumours of mice.
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Journal Article↗
Studies on adrenal histones. Characterization, biosynthesis, enzymatic phosphorylation, and acetylation of histones from a human adrenal carcinoma.
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Acetates↗
[Relationship between the DNA, RNA, histones and non-histone proteins in the nuclear fractions of cattle lymph lymphocytes under normal conditions and in lymphatic leukemia].
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Animals↗
Phosphorylation of rat thymus histones, its control and the effects thereon of gamma-irradiation.
The phosphate content of rat thymus histones was determined. As expected for a replicating tissue, histones 1 and 2B were more phosphorylated and had higher 32P uptakes than did histones from resting liver nuclei; the other histones all showed 32P uptake, but the phosphate content and uptake of histone 2A was about half that for liver histone 2A. When thymus nuclei were incubated in a slightly hypo-osmotic medium, non-histone proteins and phosphorylated histones were released into solution; this was enhanced if ATP was present in the medium. [gamma-32P]ATP was incorporated into non-histone proteins, including protein P1, and into the ADP-ribosylated form of histone 1; negligible 32P was incprporated into the other, bound, histones. Histones 1 and 2B added to the incubation medium were extensively, and histones 2A and 4 slightly, phosphorylated. Histones released by increasing the ionic strength of the medium were phosphorylated. Added lysozyme and cytochrome c were neither bound nor phosphorylated, but added non-histone protein P1 was phosphorylated, causing other histones to be released from the nuclei, especially histones 2A and 3. The released histones were phosphorylated. gamma-Irradiation decreased 32P uptake into the non-ADP-ribosylated histones 1 and 4; phosphorylation of histone 1 in vitro was unaffected. The importance of non-histone proteins, ATP availability and nuclear protein kinases to the control of histone phosphorylation in vivo is discussed.
Adenosine Triphosphate↗
Molecular characterization of the histone gene family of Caenorhabditis elegans.
The core histone genes (H2A, H2B, H3 and H4) of Caenorhabditis elegans are arranged in approximately 11 dispersed clusters and are not tandemly arrayed in the genome. Three well-characterized genomic clones, which contain histone genes, have one copy of each core histone gene per cluster. One of the clones (lambda Ceh-1) carries one histone cluster surrounded by several thousand base-pairs of non-histone DNA, and another clone (lambda Ceh-3) contains a histone cluster duplication surrounded by non-histone DNA. A third clone (lambda Ceh-2) carries a cluster of core histone genes flanked on one side (12,000 base-pairs away) by a single H2B gene and on the other by non-histone DNA. A fourth cluster (clone BE9) has one copy each of H3 and H4 and two copies each of H2A and H2B. This cluster is also flanked by non-histone DNA. Analysis of cosmid clones which overlap three of the clusters shows that no other histone clusters are closer than 8000 to 60,000 base-pairs, although unidentified non-histone transcription units are present on the flanking regions. Gene order within the histone clusters varies, and histone mRNAs are transcribed from both DNA strands. No H1 sequences are found on these core histone clones. Restriction fragment length polymorphisms between two related nematode strains (Bristol and Bergerac) were used as phenotypic markers in genetic crosses to map one histone cluster to linkage group V and another to linkage group IV. Hybridization of gene-specific probes from sea urchin to C. elegans RNA identifies C. elegans core histone messenger RNAs of sizes similar to sea urchin early stage histone mRNAs (H2A, H2B, H3 and H4). The organization of histone genes in C. elegans resembles the clustering found in most vertebrate organisms and does not resemble the tandem patterns of the early stage histone gene family of sea urchins or the major histone locus of Drosophila.
Animals↗
Isolation, identification, and characterization of histones from plasmodia of the true slime mold Physarum polycephalum using extraction with guanidine hydrochloride.
Histones from plasmodia of the true slime mold Physarum polycephalum have been prepared free of slime by an approach to histone isolation that uses extraction of nuclei with 40% guanidine hydrochloride and chromatography of the extract on Bio-Rex 70. This procedure followed by chromatography or electrophoresis has been used to obtain pure fractions of histones from Physarum microplasmodia. Physarum microplasmodia have five major histone fractions, and we show by amino acid analysis, apparent molecular weight on three gel systems containing sodium dodecyl sulfate, mobility on gels containing Triton X-100, and other characterizations that these fractions are analogous to mammalian histones H1, H2A, H2B, H3, and H4. Significant differences between Physarum and mammalian histones are noted, with histone H1 showing by far the greatest variation. Histones H1 and H4 from Physarum microplasmodia have similar, but not identical, products of partial chymotryptic digestion compared with those of calf thymus histones H1 and H4. Labeling experiments, in vivo, showed that histone H1 is the major phosphorylated histone and approximately 15 separate phosphopeptides are present in a tryptic digest of Physarum histone H1. The core histones from Physarum, histones H2A, H2B, H3, and H4, are rapidly acetylated; histone H4 shows five subfractions, analogous to the five subfractions of mammalian histone H4 (containing zero to four acetyllysine residues per molecule); histone H3 has a more complex pattern that we interpret as zero to four acetyllysine residues on each of two sequence variants of histone H3; histones H2A and H2B show less heterogeneity. Overall, the data show that Physarum microplasmodia have a set of histones that is closely analogous to mammalian histones.
Chemical Phenomena↗
Human papillomavirus type 16 E7 protein increases acetylation of histone H3 in human foreskin keratinocytes.
Histone acetylation plays an important role in chromatin remodeling and transcription control. Acetylation of histones is regulated by histone acetyltransferases and histone deacetylases (HDACs). Human papillomavirus type 16 (HPV16) E7 can inactivate retinoblastoma protein (pRB), which recruits histone deacetylases, and also physically interacts with histone acetyltransferases and histone deacetylases, suggesting E7 may affect histone acetylation. To test this, we have analyzed the state of acetylation of histone H3 in human foreskin keratinocytes. HPV16 E7 increased acetylation of histone H3 on lysine 9, which is related to transcription activation. The ability to bind both pRB and histone deacetylase was required for HPV16 E7 to increase histone acetylation. Chromatin immunoprecipitations showed HPV16 E7 increases histone acetylation on the E2F1 and cdc25A promoters. Consistent with this, RT-PCR analysis showed an increase in the expression of E2F-responsive genes involved in cell cycle control. HPV16 E7 affected neither the steady-state levels of histone acetyltransferases or deacetylases nor histone deacetylase activity. However, HPV16 E7 did increase the level of methylation of histone H3 on lysine 4, which normally requires displacement of histone deacetylase. In contrast, sodium butyrate, a known inhibitor of histone deacetylases, caused an increase in acetylated but not methylated histone H3. These data suggest HPV16 E7, by increasing histone acetylation, may create a transcriptionally active chromatin structure to promote expression of genes vital for cell cycle progression.
Acetylation↗
Prevalence and antigen specificity of anti-histone antibodies in patients with polymyositis/dermatomyositis.
Anti-histone antibodies have been detected in the sera of patients with various autoimmune diseases. The existence of anti-histone antibodies in patients with polymyositis/dermatomyositis, however, has not been reported. We found anti-histone antibodies in eight (17%) of 46 sera from patients with polymyositis/dermatomyositis by an enzyme-linked immunosorbent assay. One serum was positive for both IgG anti-histone antibodies and IgM anti-histone antibodies. Six sera were positive only for IgG anti-histone antibodies. One serum was positive only for IgM anti-histone antibodies. An indirect immunofluorescence analysis using HEp-2 cells as the substrate showed that all sera positive for anti-histone antibodies produced homogeneous nuclear fluorescence. This immunofluorescence pattern disappeared after absorption of anti-histone activity with total histones. An immunoblotting analysis demonstrated that the anti-histone antibodies were predominantly directed against histone H1 in all seven sera with IgG anti-histone antibodies. Weak reactivity with H2B and H4 were also found in three sera from the patients with polymyositis/dermatomyositis. Sera from two patients with polymyositis/dermatomyositis displayed anti-H2A and H3 activity. One of the two sera showed IgM anti-histone antibodies in the enzyme-linked immunosorbent assay reacted with H1, H2A, H2B, H3, and H4, whereas the other serum reacted with no fractions of total histones. The activity of anti-histone antibodies disappeared in immunoblotting after absorption with total histones. All of the patients with anti-histone antibodies were free from lung fibrosis or internal malignancies. Thus, our data indicate that the presence of anti-histone antibodies is classified as one of the serologic abnormalities observed in polymyositis/dermatomyositis.
Adolescent↗
Comparison of some properties of chromatin non-histone proteins and nuclear sap proteins.
The properties of rat liver and thymus non-histone and nuclear sap proteins were compared. The distribution of total, labile-bound and 0.35 M NaCl extractable non-histone proteins from one organ on polyacrylamide-gel electrophoresis in the presence of sodium dodecylsulphate is quite similar. On electrophoresis non-labelled and 32P-labelled non-histone and nuclear sap proteins from one organ differ from one another both qualitatively and quantitatively. We did not find an appreciable difference between non-labelled non-histone proteins isolated from liver and thymus. The distribution of 32P-labelled non-histone proteins from various organs differs quantitatively rather than qualitatively. Non-labelled and 32P-labelled nuclear sap proteins from liver and thymus differ significantly. 'Free' nuclear sap proteins and the proteins of ribonucleoprotein particles from thymus nuclei contain a great quantity of identical polypeptides, whereas other polypeptides are specific to each of these protein fractions. Upon incubation of nuclei with [gamma-32P]ATP the label is incorporated into all the fractions of nuclear protein. The nuclear proteins are phosphorylated at decreasing rates in the order: labile-bound non-histone proteins greater than firmly bound non-histone proteins greater than 'free' nuclear sap proteins = proteins of ribonucleoprotein particles greater than histones. Nuclear sap and non-histone proteins contain protein kinases capable of phosphorylating both these proteins and histones. Histone phosphorylation is sharply inhibited after addition of DNA, the protein kinases of nuclear sap phosphorylating less effectively the histones complexed with DNA than the non-histone proteins. Both non-histone and nuclear sap proteins contain fractions interacting in vitro with DNA. Denatured DNA binds twice as much 32P-labelled nuclear sap proteins and a little more 32P-labelled non-histone proteins than native DNA. Denatured DNA binds non-histone and nuclear sap proteins much more effectively than native DNA. It was shown by the membrane filter technique that the major part of the nuclear sap and non-histone proteins interacting with native DNA binds to it non-specifically. A certain portion of non-histone and nuclear sap proteins interacts specifically with homologous denatured DNA. The possible role of non-histone and nuclear sap proteins in the regulation of transcription is discussed.
Amino Acids↗
Transformation of sperm histone during formation and maturation of rat spermatozoa.
Changes of chromosomal basic proteins of rats have been followed during transformation of spermatids into spermatozoa in the testis and during maturation of spermatozoa in the epididymis. Rat testis chromatin has been fractionated on the basis of differing sensitivity to shearing, yielding a soluble fraction and a condensed fraction. The sperm histone is found in the condense fraction. Somatic-type histones are found in both fractions. The somatic-type histones in the condensed fraction contains much more lysine-rich histone I, than does the somatic-type histones in the soluble fraction. This may suggest that the lysine-rich histone I is the last histone to be displaced during the replacement of somatic-type histones by sperm histone. After extensive shearing followed by sucrose centrifugation, the condensed portion of testis chromatin can be further fractionated into two morphologically distinctive fractions. One is a heavy fraction possessing an elongated shape typical of the head of late spermatids. The other is a light fraction which is presumably derived from spermatids at earlier stages of chromatin condensation and which is seen as a beaded structure in the light microscope. Sperm histone of testis chromatin can be extractable completely by guanidinium chloride without a thiol, wheras 2-mercaptoethanol is required for extraction of sperm histone from caput and cauda epididymal spermatozoa. The light fraction of the condensed testis chromatin contains unmodified and monophospho-sperm histone. The sperm histones of the heavy fraction is mainly of monophospho and diphospho species, whereas unmodified and monophosphosperm histones are found in caput and cauda epididymal spermatozoa. Labeling of cysteine sulfhydryl groups of sperm histone releases by 2-mercaptoethanol treatment shows that essentially all of the cysteine residues of sperm histone in testis chromatin are present as sulfhydryl groups, while those of sperm histone isolated from mature (cauda epididymal) spermatozoa are present as disulfide forms and approximately 50% of the cysteine residues of sperm histone obtained from caput epididymal spermatozoa are in disulfide forms. These results suggest that phosphorylation of sperm histone is involved in the process of chromatin condensation during transformation of spermatozoa in the epididymis.
Animals↗
Modification of deoxyribonucleic acid-thyroid hormone receptor interaction by histones.
The effects of histones on receptor-DNA interaction were examined using an in vitro DNA-cellulose-binding assay of [125I]T3 receptor. H1 histones bound to DNA-cellulose strongly inhibited binding of receptor to DNA-cellulose. DNA-cellulose column chromatography showed that 80% of T3-binding activity attached to DNA-cellulose could be eluted using 1 mg H1 histone/ml at low ionic strength. The potent inhibitory activity of H1 histones on receptor-DNA binding was reversed by removal of H1 histones from DNA-cellulose or by removal of H1 histones from receptor. The interaction was specific for the DNA-binding activity of receptor, since H1 histones inhibit neither T3-binding activity nor core histone-binding activity of receptor. In contrast, low concentrations of core histones enhanced binding of T3 receptor to DNA-cellulose. This effect was also seen when DNA-cellulose was treated with core histones and then deprived of free core histones. The enhancement was reversed by removal of core histones bound to DNA-cellulose. A tryptic fragment of the receptor, which lost DNA-binding activity but retained hormone and core histone-binding activities, was capable of binding to DNA-cellulose in the presence of core histones. These data suggest that enhanced binding of receptor to DNA-cellulose by core histones is mediated through the core histone-binding activity of receptor. A heat-labile protein factor in nuclear extracts (possibly receptor itself) also enhanced receptor binding to DNA-cellulose. Our data suggest important roles of histones in the organization of nuclear thyroid hormone receptors in chromatin. Since H1 histone participates in condensation of chromatin and is enriched in transcriptionally inactive chromatin, inhibition of DNA-binding activity of receptor by H1 histone bound to DNA could explain the preferential binding of nuclear thyroid hormone receptor to transcriptionally active chromatin.
Animals↗
Interaction in vitro of non-epithelial intermediate filament proteins with histones.
Non-epithelial intermediate filament (IF) subunit proteins show a high and specific affinity for core histones at physiological ionic strength. When IF proteins are titrated with a mixture of core histones and linker histone H1, in general the latter is totally excluded from complexation and in the adducts formed the moderately-arginine-rich histones H2A and H2B are progressively replaced by the very-arginine-rich histones H3 and H4. At histone saturation, 2 molecules of nonneuronal IF protein bind 1 histone H1 molecule or 8 core histone molecules, whereas due to its glutamic acid-rich, C-terminal extensions one dimer of the 68 kD neurofilament protein associates with 3 molecules of histone H1 or 24 molecules of core histones. The salt stability of the insoluble association products is dependent on the amount and arginine content of the constituent histone species. Removal of the non-alpha-helical N- and C-terminal polypeptides from IF proteins by partial chymotryptic digestion does not affect their histone-binding characteristics. Since core histones are only partially inactivated by limited tryptic digestion, they also appear to react through their alpha-helix-rich central domains; the limit peptide derived from histone H1 is completely inactive at physiological ionic strength. Affinity chromatography of rod domains of IF proteins on core histone-Sepharose 4B and of histones and their limit peptides on vimentin-Sepharose 4B has shown that the interactions involving fractions of histones H3 and H4 are extremely resistant to salt and can be dissociated only with arginine or salt under denaturing conditions. In general, the experimental results revealed close parallels between the association of histones with IF proteins and their interaction with DNA.
Animals↗
Changing rates of histone mRNA synthesis and turnover in Drosophila embryos.
The rates of synthesis and turnover of histone mRNA in Drosophila embryos were determined by hybridization of in vivo and in vitro labeled embryonic RNA to Drosophila histone DNA of the recombinant plasmid cDm500. There is a large store of maternal histone mRNA, equivalent to at least 7 X 10(7) copies of each of the five classes of histone mRNA per embryo. Embryonic synthesis of histone mRNA begins at 90 min after oviposition, making the histone genes among the first to be transcribed by embryonic nuclei. Embryonic histone mRNA accumulates rapidly during the blastoderm and gastrula stages. The peak in the rate of histone mRNA synthesis per embryo coincides with the peak in the rate of DNA synthesis per embryo, which occurs at 6 hr after oviposition. After 6 hr, as the rate of DNA synthesis per embryo decreases, the rate of histone mRNA synthesis and the total mass of histone mRNA per embryo both drop sharply. The rate of histone mRNA synthesis per gene falls more than 60 fold in the first 13 hr after oviposition, from 1.3 -2.5 copies per gene-min at 2 hr to 0.02-0.03 copies per gene-min at 13 hr. From measurements of the mass of histone mRNA per embryo and of the rate of accumulation of newly synthesized histone mRNA at a number of stages of early embryogenesis we determined that the cytoplasmic half-life of histone mRNA decreases approximately 7 fold during early Drosophila development, from 2.3 hr at blastoderm to 20 min by the end of gastrulation. Thus the level of expression of histone genes in Drosophila development is controlled not only by the size of the maternal mRNA pool and changes in the rate of histone mRNA synthesis, but also by changes in the rate of histone mRNA turnover.
Animals↗
Complete displacement of somatic histones during transformation of spermatid chromatin: a model experiment.
Displacement of histones from calf thymus chromatin has been studied in an attempt to postulate the mechanisms involved in the total removal of somatic-type histones during transformation of spermatid chromatin. When chromatin is saturated with protamine (protamine/DNA, 0.5), histone I becomes displaceable at 0.15-0.3 M NaCl, suggesting that direct replacement by highly basic sperm histone could be a mechanism for its removal. While histone I is the only histone which is extensively degraded upon incubation of chromatin and, therefore, proteolysis might provide an additional mechanism for the removal of this histone, acetylation of chromatin by acetic anhydride greatly increases suscpetibility of histones IIb1, IIb2, and III to the chromosomally associated protease. These histones are extensively degraded and displaced from the DNA upon incubation of the acetylated chromatin. Although histone IV is not appreciably degraded, the proteolytic removal of acetylated histone III from chromatin weakens the interaction of acetylated histone IV to the DNA, and this histone becomes dissociable at 0.3 M NaCl. A comparison of the extent of chemical acetylation of individual histones observed in this investigation with that of enzymatic acetylation which can be achieved in vivo suggests that acetylation and proteolysis could be a mechanism for the removal of histone IIb2 and III. The displacement of histones IIb1 and IV could be explained on the basis of decreased binding to DNA as a result of their acetylation together with the proteolytic removal of their respective partner histones, IIb2 and III.
Acetylation↗
Characterization of the 55-kb mouse histone gene cluster on chromosome 3.
The histone gene cluster on mouse chromosome 3 has been isolated as a series of overlapping P1 clones, covering 110-120 kb, by probing with the histone H3-614 gene that had been mapped previously to mouse chromosome 3. There are genes for 10 core histone proteins present in a 55-kb cluster within this contig. There are three histone H3 genes, two of which are identical; four histone H2a genes, two of which are identical, one histone H4 gene; and two histone H2b genes. These histone H3 and H2a genes encode approximately 40% of the total H3 and H2a mRNA, whereas the histone H4 and histone H2b genes encode < 10% of the total H4 and H2b mRNA. There are no histone H1 genes present in this cluster. All of the histone H2a genes encode histone H2a.2 proteins (or variants of H2a.2), and account for all the H2a.2 genes in the mouse genome. All three histone H3 genes encode the histone H3.2 protein. A 21-kb region containing the adjacent H3-614 and H2a-614 genes has been duplicated and is present in an inverted repeat separated by 4.5 kb. The other two H2a genes are adjacent, with the 3' ends of their mRNAs separated by only 49 nucleotides in the DNA and the U7 snRNP binding sites separated by only 20 nucleotides. One of the histone H2b genes has lost the stem-loop sequence characteristic of the replication-dependent histone mRNAs and encodes only polyadenylated mRNAs.
Amino Acid Sequence↗
Quantitative Profiling of Histone Variants and Posttranslational Modifications by Tandem Mass Spectrometry in Arabidopsis.
Histone dynamics constitute an important layer of gene regulations associated with development and growth in multicellular eukaryotes. They also stand as key determinants of plant responses to environmental changes. Histone dynamics include the exchange of histone variants as well as post-translational modifications of their amino acid residues (such as acetylation and mono/di/trimethylation), commonly referred to as histone marks. Investigating histone dynamics with a focus on combinatorial changes occurring at their residues will greatly help unravel how plants achieve phenotypic plasticity.Mass spectrometry (MS) analysis offers unequaled resolution of the abundance of histone variants and of their marks. Indeed, relative to other techniques such as western blot or genome-wide profiling, this powerful technique allows quantifying the relative abundances of histone forms, as well as revealing coexisting marks on the same histone molecule. Yet, while MS-based histone analysis has proven efficient in several animals and other model organisms, this method stands out as more challenging in plants. One major challenge is the isolation of sufficient amounts of pure, high-quality histones, likely rendered difficult by the presence of the cell wall, for sufficiently deep and resolutive identification of histone species.In this chapter, we describe a straightforward MS-based proteomic method, implemented to characterize histone marks from Arabidopsis thaliana seedling tissues and cell culture suspensions. After acid extraction of histones, in vitro propionylation of free lysine residues, and digestion with trypsin, a treatment at highly basic pH allows obtaining sharp spectral signals of biologically relevant histone peptide forms.The method workflow described here shall be used to measure changes in histone marks between Arabidopsis thaliana genotypes, along developmental time-courses, or upon various stresses and treatments.
Histones↗
Is human histone gene expression autogenously regulated?
It has been well documented that core and H1 histone mRNAs accumulate in a manner which closely parallels the initiation of DNA synthesis and histone protein synthesis, suggesting that the onset of histone gene expression early during S phase is at least in part transcriptionally mediated. In fact, it appears that throughout S phase the synthesis of histone proteins is modulated by the availability of histone mRNAs. On the other hand, the stability of histone mRNAs and the destabilization of histone mRNAs when DNA replication is completed or inhibited are highly selective, tightly coupled and largely post-transcriptionally controlled. We present a model to account for histone mRNA turnover whereby the natural or inhibitor-induced termination of DNA replication results in an immediate loss of high affinity binding sites for newly synthesized histone proteins which in turn brings about a transient accumulation of unbound histones. These unbound histones could modify the histone translation complex, via interactions with polysomal histone mRNAs, in such a manner as to render histone mRNAs accessible to cellular ribonucleases. This type of mechanism would be operative solely at the post-transcriptional level and would be compatible with the rapid, RNA synthesis-independent destabilization of histone mRNAs which occurs following inhibition of DNA replication, as well as with the requirement for protein synthesis for histone mRNA destabilization to be initiated.
Cell Cycle↗