Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “HISTONES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMed1983

Studies on the mechanism of action of the histone kinase dependent on adenosine 3',5'-monophosphate. Fast kinetics of histone H1 phosphorylation.

The transient phase of histone H1 phosphorylation was studied by the quenched-flow method. A 'minimal' kinetic scheme of the above process was proposed. A formal kinetic analysis was given to a four-step mechanism of the reaction. Computer simulation of the transient-phase kinetics of H1 phosphorylation and the steady-state kinetics of phosphate transfer from the enzyme phosphoform to histone permitted us to estimate all kinetic constants of the proposed mechanism.

Animals↗
PubMed1988

The primary structure of the histone H2A(2) type from wheat germ. A core histone type with both, N-terminal and C-terminal extensions.

The histone H2A(2) type from wheat germ comprises at least two highly homologous isohistones with 151 amino acid residues. Microheterogeneity occurs mainly at the N-terminal and C-terminal regions. These isohistones have both N-terminal (7 amino acid residues) and C-terminal (15 amino acid residues) extensions relative to calf thymus histone H2A.

Amino Acid Sequence↗
PubMed2006

Ubp8p, a histone deubiquitinase whose association with SAGA is mediated by Sgf11p, differentially regulates lysine 4 methylation of histone H3 in vivo.

Despite recent advances in characterizing the regulation of histone H3 lysine 4 (H3-K4) methylation at the GAL1 gene by the H2B-K123-specific deubiquitinase activity of Saccharomyces cerevisiae SAGA (Spt-Ada-Gcn5-acetyltransferase)-associated Ubp8p, our knowledge on the general role of Ubp8p at the SAGA-dependent genes is lacking. For this study, using a formaldehyde-based in vivo cross-linking and chromatin immunoprecipitation (ChIP) assay, we have analyzed the role of Ubp8p in the regulation of H3-K4 methylation at three other SAGA-dependent yeast genes, namely, PHO84, ADH1, and CUP1. Like that at GAL1, H3-K4 methylation is increased at the PHO84 core promoter in the UBP8 deletion mutant. We also show that H3-K4 methylation remains invariant at the PHO84 open reading frame in the Deltaubp8 mutant, demonstrating a highly localized role of Upb8p in regulation of H3-K4 methylation at the promoter in vivo. However, unlike that at PHO84, H3-K4 methylation at the two other SAGA-dependent genes is not controlled by Ubp8p. Interestingly, Ubp8p and H3-K4 methylation are dispensable for preinitiation complex assembly at the core promoters of these genes. Our ChIP assay further demonstrates that the association of Ubp8p with SAGA is mediated by Sgf11p, consistent with recent biochemical data. Collectively, the data show that Ubp8p differentially controls H3-K4 methylation at the SAGA-dependent promoters, revealing a complex regulatory network of histone methylation in vivo.

Alcohol Dehydrogenase↗
PubMed2006

DNA methylation, histone H3 methylation, and histone H4 acetylation in the genome of a crustacean.

In this work, we used antibodies against histone H3 trimethylated at lysine 9 (H3K9m3); against histone H4 acetylated at lysines 5, 8, 12, and 16 (H4ac); and against DNA methylated at 5C cytosine (m5C) to study the presence and distribution of these markers in the genome of the isopod crustacean Asellus aquaticus. The use of these 3 antibodies to immunolabel spermatogonial metaphases yields reproducible patterns on the chromosomes of this crustacean. The X and Y chromosomes present an identical banding pattern with each of the antibodies. The heterochromatic telomeric regions and the centromeric regions are rich in H3K9m3, but depleted in m5C and H4ac. Thus, m5C does not seem to be required to stabilize the silence of these regions in this organism.

Acetylation↗
PubMed1975

Histone III. VI. Two forms of calf thymus histone III.

Microheterogeneity in the amino acid sequence of pea embryo histone III at residue 96 has been established previously. It has been indicated that calf-thymus contains two forms of histone III, with 1 or 2 residues of cysteine, respectively. Evidence is presented here that these two forms are also due to microheterogeneity at residue 96 with one form containing a cysteine residue and the other a serine residue.

Amino Acid Sequence↗
PubMedDate not supplied

Capillary electrophoresis analysis of histones, histone variants, and their post-translationally modified forms: a review.

Histones are the most intensively studied group of basic nuclear proteins and are of great importance with regard to the organization of chromatin structure and control of gene activity. The complexity of this protein family places very high demands on the analytical methods applied. The advent of high-performance capillary electrophoresis provided a promising new tool for their separation, which is an essential prerequisite for studying the biological role of this protein family. Problems inherent to histone analysis due to their unique physical and chemical properties are reviewed, and the pros and cons of distinct strategies developed for CE separation of these proteins are discussed.

Buffers↗
PubMed1978

[Antisera to individual histone fractions of the calf thymus. II. A study of the immunochemical specificity of the histones by an indirect immunofluorescence method].

Immune antisera to 5 fractions (H1, H2a, H2b, H3, H4) of calf thymus histone were assayed using indirect immunofluorescence (IIF). The analysis of such sera by this technique, as well as the data on complement fixation obtained previously, show that these antisera are highly active and specific for various test-objects: thymys, liver nuclei of rat, chicken, and calf, chicken erythrocytes, metaphase chromosomes of mouse fibroblasts. These antisera are of importance for the evaluation of species- and tissue-specificity of different histone fractions. Using the IIF reaction, a comparison was made between the nucleosome fraction H3, which is evolutionary stable, and fraction HI from calf thymus, rat and chicken liver, and chicken erythrocytes.

Animals↗
PubMed1987

Non-histone chromosomal protein HMG1 modulates the histone H1-induced condensation of DNA.

Circular dichroic spectra revealed that the previously known regular, asymmetric condensation of DNA by H1 histone was modulated by HMG1, a nonhistone chromosomal protein. Under approximately physiological salt and pH conditions (150 mM NaCl, pH 7), ellipticities at 270 nm were observed as follows: DNA, 9 X 10(3) degree, cm2/dmol nucleotide; DNA X H1 histone complex (1:0.4, w/w), -37 X 10(3) degree, cm2/dmol nucleotide, and DNA X H1 X HMG1 complex (1:0.4:0.4 w/w/w), -52 X 10(3) degree, cm2/dmol. HMG1 by itself did not distort the spectrum of DNA, showing that the effect of HMG1 on the DNA X H1 complex was not simply the summation of individual effects of HMG1 and H1 on the DNA spectrum. The effect of added HMG1 on the spectrum of the preformed DNA X H1 complex depended on the amount of HMG1 added and developed slowly (a day) as if a structure required annealing. The ternary complex, DNA X HMG1 X 1, seemed to represent a specific structure, since its formation depeNded on the reduced sulfhydryl state of HMG1; the disulfide form of HMG1, which was shown by circular dichroism to contain more random coil than did the reduced form, had no effect on the circular dichroic spectrum of the DNA X H1 complex.

Animals↗
PubMed1979

[Biochemical studies on histones of the central nervous system. I. Characterization and partial identification of the label of histones from rat brain following intraventricular administration of 1-[14C]-acetate].

Rat brain histones were acetylated in vivo by intraventricular injection of [14C]-acetate. More than 90% of the label is the result of a true acetylation. Enzymatic proteolysis of the labelled histone fraction and subsequent chromatographic investigation of the digestion products showed about 60% of the recovered radioactive material to be epsilon-acetyl lysine, whereas 22% of the radioactivity was found in an unidentified spot.

Acetates↗
PubMed1977

Studies of human histone messenger RNA. I. Methods for the isolation and partial characterization of RNA fractions containing human histone message from HeLa S3 polyribosomes.

Large quantities of nonpolyadenylated [poly(A(-))] 4 to 18 S RNA were isolated from the polyribosomes of S phase HeLa S3 cells and were fractionated into multiple discrete RNA components by continuous elution preparative electrophoresis. Previous studies have shown that treatment os S phase HeLa cells with cytosine arabinoside inhibits DNA replication and causes translatable histone messenger RNA (mRNA) species to disappear from cytoplasmic polyribosomes (Borun, T. W., Scharff, M.D., and Robbins, E. (1967) Proc. Natl. Acad. Sci. U.S.A. 58, 1977-1983; Gallwitz, D., and Mueller, G. C. (1969) J. Biol. Chem. 244, 5948-5952; Borun, T. W., Gabrielli, F., Ajiro, K., Zweidler, A., and Baglioni, C. (1975) Cell 4, 59-67; Gallwitz, D. (1975) Nature 257, 247-248). In the present study it was found that cytosine arabinoside treatment does not appreciably affect major 7.5 to 8 S RNA species but does cause the disappearance of 8.6 to 13 S RNA components from preparative electrophoresis elution profiles of S phase polyribosomal 4 to 18 S RNA. Base ratio analysis of the 8.6 to 13 S putative histone mRNA species indicates that they are GC-rich but not like the HeLa 18 or 28 S rRNA in base composition.

Chromatography, Affinity↗
PubMed1993

Functional complementarity between the HMG1-like yeast mitochondrial histone HM and the bacterial histone-like protein HU.

The mitochondrial histone HM is the major DNA-binding protein in mitochondria and is necessary for maintenance of the mitochondrial genome in the yeast Saccharomyces cerevisiae during growth on fermentable sugars. HM and the Escherichia coli histone-like protein HU have similar activities in vitro, including DNA supercoiling, but share no sequence similarity. We show that HU can functionally complement the respiration deficiency associated with yeast strains lacking HM. Conversely, phenotypes of E. coli cells lacking HU protein, including nucleoid loss and a filamentous cell morphology, were alleviated by expression of HM in these cells. The HU protein of bacteria and the HM protein of mitochondria are therefore functionally complementary in vivo. Functional similarities among HM, HU, and the nuclear HMG1 proteins are implicated and discussed.

Bacterial Proteins↗
PubMed2005

Inhibition of histone deacetylase 2 increases apoptosis and p21Cip1/WAF1 expression, independent of histone deacetylase 1.

Histone deacetylases (HDACs) 1 and 2 share a high degree of homology and coexist within the same protein complexes. Despite their close association, each possesses unique functions. We show that the upregulation of HDAC2 in colorectal cancer occurred early at the polyp stage, was more robust and occurred more frequently than HDAC1. Similarly, while the expression of HDACs1 and 2 were increased in cervical dysplasia and invasive carcinoma, HDAC2 expression showed a clear demarcation of high-intensity staining at the transition region of dysplasia compared to HDAC1. Upon HDAC2 knockdown, cells displayed an increased number of cellular extensions reminiscent of cell differentiation. There was also an increase in apoptosis, associated with increased p21Cip1/WAF1 expression that was independent of p53. These results suggest that HDACs, especially HDAC2, are important enzymes involved in the early events of carcinogenesis, making them candidate markers for tumor progression and targets for cancer therapy.

Apoptosis↗
PubMed2004

Selective regulation of class I and class II histone deacetylases expression by inhibitors of histone deacetylases in cultured mouse neural cells.

The expression of 10 histone deacetylases (HDAC1-10) mRNAs in mouse neuroblastoma Neuro-2a and microglia N9 cell cultures after treatment by inhibitors of HDACs, sodium butyrate and trichostatin A was studied to elucidate whether HDAC inhibitors affect the gene expression of HDACs themselves. Northern blot analysis demonstrated two- to four-fold elevated levels of mRNAs for HDAC1, -3, -5, and -6 after drug treatment in comparison with untreated cells, while mRNA levels for HDAC2 and -7 did not change significantly. In both Neuro-2a and N9 cells the highest increase was observed for HDAC5 and -6 mRNA, whereas, HDAC4 had a prominent increase in mRNA levels after drug treatment only in N9 microglia cell line but not in Neuro-2a. Immunocytochemical examination confirmed that changes in protein levels of HDACs were similar to changes in their mRNA levels. There exists an auto-regulatory feedback loop to the expression levels of several HDACs after inhibition of their biochemical activity, adding several HDAC genes to the list of genes regulated by HDAC inhibitors.

Animals↗
PubMed2006

5-Aza-2'-deoxycytidine-mediated reductions in G9A histone methyltransferase and histone H3 K9 di-methylation levels are linked to tumor suppressor gene reactivation.

The epigenetic silencing of tumor suppressor genes is a common event during carcinogenesis, and often involves aberrant DNA methylation and histone modification of gene regulatory regions, resulting in the formation of a transcriptionally repressive chromatin state. Two examples include the antimetastatic, tumor suppressor genes, desmocollin 3 (DSC3) and MASPIN, which are frequently silenced in this manner in human breast cancer. Treatment of the breast tumor cell lines MDA-MB-231 and UACC 1179 with 5-aza-2'-deoxycytidine (5-aza-CdR) induced transcriptional reactivation of both genes in a dose-dependent manner. Importantly, DSC3 and MASPIN reactivation was closely and consistently linked with significant decreases in promoter H3 K9 di-methylation. Moreover, 5-aza-CdR treatment also resulted in global decreases in H3 K9 di-methylation, an effect that was linked to its ability to mediate dose-dependent, post-transcriptional decreases in the key enzyme responsible for this epigenetic modification, G9A. Finally, small interfering RNA (siRNA)-mediated knockdown of G9A and DNMT1 led to increased MASPIN expression in MDA-MB-231 cells, to levels that were supra-additive, verifying the importance of these enzymes in maintaining multiple layers of epigenetic repression in breast tumor cells. These results highlight an additional, complimentary mechanism of action for 5-aza-CdR in the reactivation of epigenetically silenced genes, in a manner that is independent of its effects on DNA methylation, further supporting an important role for H3 K9 methylation in the aberrant repression of tumor suppressor genes in human cancer.

Azacitidine↗
PubMed2005

Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors.

The hydroxamic acid (HAA) analogue pan-histone deacetylase (HDAC) inhibitors (HDIs) LAQ824 and LBH589 have been shown to induce acetylation and inhibit the ATP binding and chaperone function of heat shock protein (HSP) 90. This promotes the polyubiquitylation and degradation of the pro-growth and pro-survival client proteins Bcr-Abl, mutant FLT-3, c-Raf, and AKT in human leukemia cells. HDAC6 is a member of the class IIB HDACs. It is predominantly cytosolic, microtubule-associated alpha-tubulin deacetylase that is also known to promote aggresome inclusion of the misfolded polyubiquitylated proteins. Here we demonstrate that in the Bcr-abl oncogene expressing human leukemia K562 cells, HDAC6 can be co-immunoprecipitated with HSP90, and the knock-down of HDAC6 by its siRNA induced the acetylation of HSP90 and alpha-tubulin. Depletion of HDAC6 levels also inhibited the binding of HSP90 to ATP, reduced the chaperone association of HSP90 with its client proteins, e.g. Bcr-Abl, and induced polyubiquitylation and partial depletion of Bcr-Abl. Conversely, the ectopic overexpression of HDAC6 inhibited LAQ824-induced acetylation of HSP90 and alpha-tubulin and reduced LAQ824-mediated depletion of Bcr-Abl, AKT, and c-Raf. Collectively, these findings indicate that HDAC6 is also an HSP90 deacetylase. Targeted inhibition of HDAC6 leads to acetylation of HSP90 and disruption of its chaperone function, resulting in polyubiquitylation and depletion of pro-growth and pro-survival HSP90 client proteins including Bcr-Abl. Depletion of HDAC6 sensitized human leukemia cells to HAA-HDIs and proteasome inhibitors.

Acetylation↗
PubMed2000

Cell signaling switches HOX-PBX complexes from repressors to activators of transcription mediated by histone deacetylases and histone acetyltransferases.

The Hoxb1 autoregulatory element comprises three HOX-PBX binding sites. Despite the presence of HOXB1 and PBX1, this enhancer fails to activate reporter gene expression in retinoic acid-treated P19 cell monolayers. Activation requires cell aggregation in addition to RA. This suggests that HOX-PBX complexes may repress transcription under some conditions. Consistent with this, multimerized HOX-PBX binding sites repress reporter gene expression in HEK293 cells. We provide a mechanistic basis for repressor function by demonstrating that a corepressor complex, including histone deacetylases (HDACs) 1 and 3, mSIN3B, and N-CoR/SMRT, interacts with PBX1A. We map a site of interaction with HDAC1 to the PBX1 N terminus and show that the PBX partner is required for repression by the HOX-PBX complex. Treatment with the deacetylase inhibitor trichostatin A not only relieves repression but also converts the HOX-PBX complex to a net activator of transcription. We show that this activation function is mediated by the recruitment of the coactivator CREB-binding protein by the HOX partner. Interestingly, HOX-PBX complexes are switched from transcriptional repressors to activators in response to protein kinase A signaling or cell aggregation. Together, our results suggest a model whereby the HOX-PBX complex can act as a repressor or activator of transcription via association with corepressors and coactivators. The model implies that cell signaling is a direct determinant of HOX-PBX function in the patterning of the animal embryo.

Acetyltransferases↗
PubMed2005

Epigenetics--an epicenter of gene regulation: histones and histone-modifying enzymes.

The treatment of cancer through the development of new therapies is one of the most important challenges of our time. The decoding of the human genome has yielded important insights into the molecular basis of physical disorders, and in most cases a connection between failures in specific genes and the resulting clinical symptoms can be made. The modulation of epigenetic mechanisms enables, by definition, the alteration of cellular phenotype without altering the genotype. The information content of a single gene can be crucial or harmful, but the prerequisite for a cellular effect is active gene transcription. To this end, epigenetic mechanisms play a very important role, and the transcription of a given gene is directly influenced by the modification pattern of the surrounding histone proteins as well as the methylation pattern of the DNA. These processes are effected by different enzymes which can be directly influenced through the development of specific modulators. Of course, all genetic information is written as a four-character code in DNA. However, epigenetics describes the art of reading between the lines.

Acetylation↗
PubMed2006

SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis.

The mammalian cytoplasmic protein SirT2 is a member of the Sir2 family of NAD+-dependent protein deacetylases involved in caloric restriction-dependent life span extension. We found that SirT2 and its yeast counterpart Hst2 have a strong preference for histone H4K16Ac in their deacetylation activity in vitro and in vivo. We have pinpointed the decrease in global levels of H4K16Ac during the mammalian cell cycle to the G2/M transition that coincides with SirT2 localization on chromatin. Mouse embryonic fibroblasts (MEFs) deficient for SirT2 show higher levels of H4K16Ac in mitosis, in contrast to the normal levels exhibited by SirT1-deficient MEFs. The enzymatic conversion of H4K16Ac to its deacetylated form may be pivotal to the formation of condensed chromatin. Thus, SirT2 is a major contributor to this enzymatic conversion at the time in the cell's life cycle when condensed chromatin must be generated anew.

Animals↗