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Results for “Histone Modifications”

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At least 109 records · Page 6Linked to original sources
PubMed2004

17beta-Estradiol inhibits class II major histocompatibility complex (MHC) expression: influence on histone modifications and cbp recruitment to the class II MHC promoter.

Major histocompatibility complex (MHC) class II proteins are important for the initiation of immune responses and are essential for specific recognition of foreign antigens by the immune system. Regulation of class II MHC expression primarily occurs at the transcriptional level. The class II transactivator protein is the master regulator that is essential for both constitutive and interferon-gamma-inducible class II MHC expression. Estrogen [17beta-estradiol (17beta-E2)] has been shown to have immunomodulatory effects. In this study, we show that 17beta-E2 down-regulates interferon-gamma inducible class II MHC protein levels on brain endothelial cells, as well as other cell types (astrocytes, fibrosacroma cells, macrophages). The inhibitory effects of 17beta-E2 on class II MHC expression are not due to changes in class II transactivator mRNA or protein levels, rather, 17beta-E2 mediates inhibition at the level of class II MHC gene expression. We demonstrate that 17beta-E2 attenuates H3 and H4 histone acetylation and cAMP response element binding protein-binding protein association with the class II MHC promoter, suggesting that 17beta-E2 inhibits class II MHC expression by a novel mechanism involving modification of the histone acetylation status of the class II MHC promoter.

Acetylation↗
PubMed2002

Dependence of histone modifications and gene expression on DNA hypermethylation in cancer.

We examined the relationship between aberrant DNA hypermethylation and key histone code components at a hypermethylated, silenced tumor suppressor gene promoter in human cancer. In lower eukaryotes, methylated H3-lysine 9 (methyl-H3-K9) determines DNA methylation and correlates with repressed gene transcription. Here we show that a zone of deacetylated histone H3 plus methyl-H3-K9 surrounds a hypermethylated, silenced hMLH1 promoter, which, when unmethylated and active, is embedded in methyl-H3-K4 and acetylated H3. Inhibiting DNA methyltransferases, but not histone deacetylases, leads first to promoter demethylation, second to gene reexpression, and finally to complete histone code reversal. Our findings suggest a new paradigm-DNA methylation may directly, or indirectly by inhibiting transcription, maintain key repressive elements of the histone code at a hypermethylated gene promoter in cancer.

Acetylation↗
PubMed1975

Histone modification in liver after administration of inducers of mixed function oxidase activity.

The phosphorylation and acetylation of rat liver histones in vivo were determined after administration of phenobarbital or 3-methylcholanthrene. No changes were observed in the phosphorylation profile of histones separated by gel electrophoresis after treatment with either of these two inducing agents. However, after 2h of treatment with either phenobarbital or 3-methylcholanthrene, a significant increase in acetylation of histones was noted, particularly in the F2a1 and (F3, F2b, F2a2) regions. It is suggested that this increase which precedes the enhancement in RNA synthesis may play a role in the alteration of transcription in liver.

Acetates↗
PubMed2003

Global control of histone modification by the anaphase-promoting complex.

Acetylation and phosphorylation of the amino-terminal tails of the core histones fluctuate on a global scale in concert with other major events in chromosome metabolism. A ubiquitin ligase, the anaphase-promoting complex (APC), controls events in chromosome metabolism such as sister chromatid cohesion and may regulate H3 phosphorylation by targeting Aurora A, one of several S10-directed H3 kinases in vertebrate cells, for destruction by the proteasome. Our analysis of apc10Delta and apc11(ts) loss-of-function mutants reveals that the APC controls the global level of H3 S10 phosphorylation in cycling yeast cells. Surprisingly, it also regulates dephosphorylation of H3 and global deacetylation of H2B, H3, and H4 during exit from the cell cycle into G(0). Genetic, biochemical, and microarray analyses suggest that APC-dependent cell cycle control of H3 phosphorylation is exerted at the level of an Aurora H3 kinase, Ipl1p, while APC-dependent transcriptional induction of GLC7, an essential H3 phosphatase, contributes to sustained H3 dephosphorylation upon cell cycle withdrawal. Collectively, our results establish that core histone acetylation state and H3 phosphorylation are physiologically regulated by the APC and suggest a model in which global reconfiguration of H3 phosphorylation state involves APC-dependent control of both an H3 kinase and a conserved phosphatase.

Acetylation↗
PubMed1983

Extent of histone modifications and H1(0) content during cell cycle progression in the presence of butyrate.

The effects of butyrate upon the extents of phosphorylation of histones H1 and H1(0) during cell-cycle progression have been investigated. Chinese hamster (line CHO) cells were synchronized in early S phase and released into medium containing 0 or 15 mM butyrate to resume cell-cycle traverse into G1 of the next cell cycle. Cells were also mechanically selected from monolayer cultures grown in the presence of colcemid and 0 or 15 mM butyrate to obtain greater than 98% pure populations of metaphase cells. Although cell cycle progression is altered by butyrate, electrophoretic patterns of histones H1, H1(0), H3, and H4 indicate that butyrate has little, if any, effect on the extents of H1 and H1(0) phosphorylation during the cell cycle or the mitotic-specific phosphorylation of histone H3. Butyrate does, however, inhibit removal of extraordinary levels of histone H4 acetylation (hyperacetylation) during metaphase, and it appears to cause an increase in the content of H1(0) in chromatin during the S or G2 phases of the cell cycle.

Acetylation↗
PubMed1987

Histone modifications accompanying the onset of developmental commitment.

In the sea urchin, Strongylocentrotus purpuratus, three cell types comprise the 16-cell stage embryo: micromeres, macromeres, and mesomeres. We have analyzed these three cell types for nuclear proteins that were synthesized during the earliest stages of embryonic development. The most striking differences in composition of newly synthesized proteins were found between the micromeres, which are the most committed cell type, and the macromeres and mesomeres. First, the micromeres lacked triply modified forms of histone H3; the levels of doubly modified forms of H3 were also greatly reduced. In contrast, micromeres were enriched in a band which migrated at the position of unmodified, unacetylated, histone H3 protein. Second, the overall distribution of H2A histone variants differed among the three cell types. Compared with macromeres and mesomeres, micromeres had a higher ratio of alpha-stage to cleavage-stage (CS) histone H2A; the micromere nuclei were depleted by 50 and 35%, respectively, in embryonically synthesized histone CS-H2A. Third, micromeres displayed different profiles of H1 histones. (a) They contained a cleavage-stage H1 histone which migrated faster than that of macromeres and mesomeres. This protein displays the electrophoretic behavior expected for a protein with reduced levels of posttranslational covalent modification. (b) Micromeres also had reduced levels of an H1 histone (designated H1 alpha a) band found in the alpha-H1 region of macromeres and mesomeres. These changes in chromatin modification correlate with the degree of commitment of cells in the developing embryo; they may reflect differing activities of the chromatin modifying enzymes in the various cell types at the 16-cell stage. Thus, the newly synthesized chromatin proteins of the individual blastomere types already differ in the developing sea urchin by the 16-cell stage. We suggest that variations in histone subtypes and in the levels of activity of chromatin modifying enzymes, e.g., acetylases and phosphorylases, could be involved in commitment and differentiation of different cell types.

Acetylation↗
PubMed1992

Reversible histone modifications and the chromosome cell cycle.

During the eukaryotic cell cycle, chromosomes undergo large structural transitions and spatial rearrangements that are associated with the major cell functions of genome replication, transcription and chromosome condensation to metaphase chromosomes. Eukaryotic cells have evolved cell cycle dependent processes that modulate histone:DNA interactions in chromosomes. These are; i) acetylations of lysines; ii) phosphorylations of serines and threonines and iii) ubiquitinations of lysines. All of these reversible modifications are contained in the well-defined very basic N- and C-terminal domains of histones. Acetylations and phosphorylations markedly affect the charge densities of these domains whereas ubiquitination adds a bulky globular protein, ubiquitin, to lysines in the C-terminal tails of H2A and H2B. Histone acetylations are strictly associated with genome replication and transcription; histone H1 and H3 phosphorylations correlate with the process of chromosome condensation. The subunits of histone H1 kinase have now been shown to be cyclins and the p34CDC2 kinase product of the cell cycle control gene CDC2. It is probable that all of the processes that control chromosome structure:function relationships are also involved in the control of the cell cycle.

Acetylation↗