High impact information on His3:CG31613

• PcG-bound chromatin is trimethylated at histone H3 Lys27 and is generally transcriptionally silent [1].
• These findings indicate that histone H3 K56 acetylation at the entry-exit gate enables recruitment of the SWI/SNF nucleosome remodeling complex and so regulates gene activity [2].
• We report lysine 56 in histone H3 as a novel acetylation site that is located in the globular domain, where it extends toward the DNA major groove at the entry-exit points of the DNA superhelix as it wraps around the nucleosome [2].
• Acetylation in histone H3 globular domain regulates gene expression in yeast [2].
• Suv39h1 and Suv39h2 govern methylation of histone H3 Lys9 (H3-Lys9) in heterochromatic regions [3].

Biological context of His3:CG31613

• His2Av mutants show reduced acetylation of histone H4 at Lys 12, decreased methylation of histone H3 at Lys 9, and a reduction in HP1 recruitment to the centromeric region [4].
• Here, we provide evidence for the sequential binding of PcG proteins at a Polycomb response element (PRE) in proliferating cells in which the sequence-specific DNA binding Pho and Phol proteins directly recruit E(z)-containing complexes, which in turn methylate histone H3 at lysine 27 (H3mK27) [5].
• To understand the molecular mechanism of the methyl-Lys 27 histone code recognition, we have determined a 1.4-A-resolution structure of the chromodomain of Polycomb in complex with a histone H3 peptide trimethylated at Lys 27 [6].
• Mouse PRC2 (mPRC2) has been implicated in X inactivation, as mPRC2 proteins transiently accumulate on the inactive X chromosome (Xi) at the onset of X inactivation to methylate histone H3 lysine 27 (H3-K27) [7].
• Recently, one mechanism of HP1 chromosome association was revealed; the amino-terminal chromo domain of HP1 interacts with methylated lysine nine of histone H3, consistent with the histone code hypothesis [8].

Anatomical context of His3:CG31613

• Using immunoprecipitation of in vivo formaldehyde-fixed chromatin in phenotypically diverse cultured cell lines, we have mapped PRC1 components, the histone methyl transferase (HMT) Enhancer of zeste (E(z)) and histone H3 modifications in active and inactive PcG-controlled regions [9].
• We further show that germ cells lacking pgc show increased levels of K4, but not K9 histone H3 methylation, and that the chromatin remodeling Swi/Snf complex is required for a second stage in germ cell transcriptional repression [10].
• Homozygous incenp(EC3747) embryos show absence of phosphorylation of histone H3 in mitosis, failure of cytokinesis and polyploidy, and defects in peripheral nervous system development [11].
• The antisense RNA of histone H3 is synthesized exclusively in testes [12].

Associations of His3:CG31613 with chemical compounds

• We show that this complex contains a methyltransferase activity that methylates lysine 9 and lysine 27 of histone H3, but the activity is lost when the E(Z) SET domain is mutated [13].
• Surprisingly, whereas localization of centromere proteins is unaltered, the focal, G(2)-specific distribution of phosphorylated histone H3 at serine 10 (phosH3) is dispersed in these cells [14].
• Matching patterns of permanganate reactivity are also observed for a non-heat shock promoter, the histone H3 promoter [15].
• These stress-induced changes in the methylation level of the N-terminal proline residue of histone H2B and shift in the methylation sites of histone H3 may be involved in the restructuration of chromatin accompanying the inactivation of normal genes in response to stress [16].
• We found that this enzyme is an arginine-directed kinase that can phosphorylate histone H3 at serines 10 and 28 in vitro, suggesting that human Aurora-B is a mitotic histone H3 kinase [17].

Physical interactions of His3:CG31613

• Histone H3 methylated in vitro by the E(Z)/ESC complex binds specifically to Polycomb protein [13].
• In vitro, all three HP1s bind to tailed and tailless nucleosomes and specifically interact with the histone-fold of histone H3 [18].
• A trithorax-group complex purified from Saccharomyces cerevisiae is required for methylation of histone H3 [19].

Enzymatic interactions of His3:CG31613

• Aurora-B phosphorylates Histone H3 at serine28 with regard to the mitotic chromosome condensation [20].
• The JIL-1 kinase localizes to interband regions of Drosophila polytene chromosomes and phosphorylates histone H3 Ser10 [21].

Regulatory relationships of His3:CG31613

• Mutations designed to mimic hyper-phosphorylation render the protein incapable of binding HOAP and the DmORC1 subunit but confer enhanced homo-dimerization and lysine 9-methylated histone H3-binding to the protein [22].
• Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly [23].

Other interactions of His3:CG31613

• Recombinant complexes containing ESCL in place of ESC can methylate histone H3 with activity levels, and lysine specificity for K27, similar to that of the ESC-containing complex [24].
• Full-length dSU(VAR)3-9 specifically methylates lysine 9 within histone H3 on peptides, on intact histones, and, to a lesser extent, on nucleosomes [25].
• A similar mechanism in heterochromatin assembly is mediated by HP1, a chromodomain protein that binds to histone H3 methylated at Lys 9 [6].
• Stable transcriptional repression did not correlate with maintenance of YY1 or Polycomb DNA binding, but did correlate with persistence of histone H3 methylation on lysine 27 [26].
• In vitro binding assay results indicate that the MRG15 chromo domain can bind to methylated Lys36, but not methylated Lys4, Lys9 and Lys27 of histone H3 [27].

Analytical, diagnostic and therapeutic context of His3:CG31613

• Furthermore, using chromatin immunoprecipitation assays, we show that disruption of CENP-B homologs causes a decrease in heterochromatin-specific modifications of histone H3 [28].
• Characterization of chicken CENP-A and comparative sequence analysis of vertebrate centromere-specific histone H3-like proteins [29].
• Moreover, the quantitative real-time PCR confirmed that the HDI-induced hyperacetylation of histone H3 enhanced both the basal and the inducible expression of hsp70 mRNA level [30].
• These include the collection of embryos and larvae, irradiation with x-rays to damage DNA, and fixing and staining of tissues with an antibody to phosphorylated histone H3 to measure the mitotic index [31].

References