Disease relevance of H3

• H3 and the mutant variants selected with mAbs 36.2.2 (H3-36) and 54.2.8 (H3-54) induced severe myocarditis in DBA/2 (H-2d) and A/J (H-2a) male mice, whereas CBA (H-2k) mice were disease resistant [1].
• 4) Identifying this gene and an adjacent H3 gene as being of the fully replication-dependent expression class, by measuring changes in the steady state levels of their mRNAs in the presence of hydroxyurea and during differentiation of murine erythroleukemia cells [2].
• Because mitogenesis by H3 viruses is not I-E dependent, it appears that influenza A viruses stimulate B cell mitogenesis by at least two different mechanisms [3].
• The determinants recognized by helper T cells specific for the site E region of H3 subtype influenza virus hemagglutinin (HA) have been defined by examining the reactivity of T-cell clones with sets of overlapping peptides of various lengths covering the site [4].
• A gene linked to a minor histocompatibility locus (H-3) on the second chromosome also influences susceptibility to glucocorticoid- and phenytoin-induced cleft palate [5].

High impact information on H3

• Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9 [6].
• Methylation of lysine 9 in histone H3 is recognized by heterochromatin protein 1 (HP1), which directs the binding of other proteins to control chromatin structure and gene expression [6].
• Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins [7].
• Here we show that mammalian methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h HMTases) generate a binding site for HP1 proteins--a family of heterochromatic adaptor molecules implicated in both gene silencing and supra-nucleosomal chromatin structure [7].
• The two forms differ at a single amino acid at position 85, the gene (beta 2m) is located on chromosome 2 linked to a minor histocompatibility (H) region, H-3 [8].

Chemical compound and disease context of H3

• Phosphorylation of histone H3 at serine 10 is indispensable for neoplastic cell transformation [9].
• Lysine-specific murine histone H3 methyltransferase, G9a, was expressed and purified in a baculovirus expression system [10].

Biological context of H3

• The H3 complex, on mouse Chromosome 2, is an important model locus for understanding mechanisms underlying non-self Ag recognition during tissue transplantation rejection between MHC-matched mouse strains [11].
• The H3 complex spans a region that shows conserved synteny to human chromosomes 15q, 2q, and 20p [12].
• A monoclonal antibody has been developed that recognizes a mouse lymphocyte antigen, Ly-23, that is controlled by an H-3 histocompatibility complex-linked gene on the second chromosome [13].
• Competitive binding experiments demonstrate that this antigen is distinct from the polymorphic beta 2-microglobulin antigen, which also is encoded by a gene closely linked to H-3 [13].
• The classical minor histocompatibility 3 (H3) locus was originally defined by the phenotype of skin graft rejection, which is a complex genetic trait [12].

Anatomical context of H3

• H3a is a minor histocompatibility Ag gene, located within H3, that encodes a polymorphic peptide alloantigen recognized by cytolytic T cells [11].
• A lymphocyte antigen encoded by a locus closely linked to H-3 on the second chromosome of the mouse [13].
• Both class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) and class II MHC-restricted helper T cells (TH) specific for antigens encoded by genes within the H-3 locus were isolated and analyzed [14].
• The hypothesis was investigated that suppressor cells may be responsible for maintenance of immunologic tolerance of a minor H3 antigen in mice that express the antigen naturally [15].
• We introduced modified mouse histone H3 genes into mouse fibroblasts and studied the regulation of several different H3 mRNAs that are not terminated with a normal histone 3' end [16].

Associations of H3 with chemical compounds

• Viruses isolated early in the evolution of the H3 subtype (from 1968 to 1971) are relatively weak mitogens and recognize the sequence N-acetylneuraminic acid alpha 2,6 galactose (NeuAc alpha 2,6Gal) but not NeuGc alpha 2,6Gal [17].
• Distinct differences in receptor-binding specificity were observed between strongly and weakly mitogenic viruses of the H3 subtype, with strong mitogenic activity correlating with the ability of the virus to recognize the sequence N-glycolylneuraminic acid alpha 2,6 galactose (NeuGc alpha 2,6Gal) [17].
• Furthermore, like the intact virus, HA of the H2 (but not H3) subtype is mitogenic only for B cells expressing the class II major histocompatibility complex glycoprotein I-E [18].
• In eukaryotes, histone H3 trimethylated at lysine 4 (H3K4me3) is associated with active chromatin and gene expression [19].
• Phosphorylation at a highly conserved serine residue (Ser-10) in the histone H3 tail is considered to be a crucial event for the onset of mitosis [20].

Physical interactions of H3

• The histone H3 gene on chromosome 3 has multiple potential binding sites for the Sp1 transcription factor [21].

Enzymatic interactions of H3

• Furthermore, assays with Rsk-2 showed that this kinase phosphorylates H2B but not H3 in vitro [22].
• We propose that persistent activation of the Ras-MAPK pathway and MSK1 resulting in the elevation of phosphorylated H3 levels may contribute to the aberrant gene expression observed in the oncogene-transformed cells [22].

Regulatory relationships of H3

• A 15-kDa protein detected initially in amyloidotic ileum from a transgenic mouse and subsequently in control (nontransgenic) ileum by various polyclonal rabbit antiserums applied to electroblots of extracts derived from these tissues was identified by partial sequence analysis as histone H3 [23].

Other interactions of H3

• The restriction of the response to the H-3 antigen requires effector-target identity of the H-2D molecule but not the B2M molecule of the class I antigen [24].
• Another gene affecting this trait is closely linked to the H-3 and Ir-2 loci on the second chromosome [25].
• Evidence for linkage of murine beta 2-microglobulin to H-3 and Ly-4 [26].
• We exploited a unique positional cloning approach relying on the potent negative selection capability of cytotoxic T cells to identify the H3a gene responsible for immunodominant H2-Db-restricted determinants of the classically defined mouse autosomal H3 complex [27].
• MD simulations of H2+H3 shows that the second half of H2 (residues 184-194) and parts of H3 (residues 200-204 and 215-223) undergo a transition from alpha-helical conformation to a beta and/or random coil state [28].

Analytical, diagnostic and therapeutic context of H3

• The strain distribution pattern distinguished Ly-m11 from any known murine lymphocyte alloantigens, but it follows the H-3 alpha haplotype which is defined by skin transplantation [29].
• METHODS AND RESULTS: Corneal allograft survival and the role of CD4+ T cells and CD8+ T cells were examined in corneal transplants that expressed genetically defined minor H3 alloantigens [30].
• Antiserums were made against immunogens unrelated to the histone, but they recognized calf thymus histone H3 (14.7 kDa) on Western blots [23].
• The rate of H3 gene transcription decreased by only 35% after treatment with cytosine arabinoside [31].
• Chromatin immunoprecipitation assays revealed that histone H3 methylated at lysine-9, a hallmark of condensed heterochromatin, was enriched at the methylated transposon, whereas the unmethylated transposon formed a relaxed euchromatin structure, as evidenced by enrichment of acetylated histone H3 and reporter gene expression [32].

References