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Gene Review

H3  -  histocompatibility 3

Mus musculus

Synonyms: H-3
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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


Biological context of H3


Anatomical context of H3


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


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].


  1. Alterations in major histocompatibility complex association of myocarditis induced by coxsackievirus B3 mutants selected with monoclonal antibodies to group A streptococci. Huber, S.A., Moraska, A., Cunningham, M. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  2. Isolation and characterization of a mouse fully replication-dependent H1 gene within a genomic cluster of core histone genes. Yang, Y.S., Brown, D.T., Wellman, S.E., Sittman, D.B. J. Biol. Chem. (1987) [Pubmed]
  3. Influenza viruses as lymphocyte mitogens. I. B cell mitogenesis by influenza A viruses of the H2 and H6 subtypes is controlled by the I-E/C subregion of the major histocompatibility complex. Scalzo, A.A., Anders, E.M. J. Immunol. (1985) [Pubmed]
  4. Conservation of determinants for class II-restricted T cells within site E of influenza virus hemagglutinin and factors influencing their expression. Brown, L.E., White, D.O., Jackson, D.C. J. Virol. (1993) [Pubmed]
  5. Biochemical mechanism of glucocorticoid-and phenytoin-induced cleft palate. Goldman, A.S. Curr. Top. Dev. Biol. (1984) [Pubmed]
  6. Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9. Nielsen, P.R., Nietlispach, D., Mott, H.R., Callaghan, J., Bannister, A., Kouzarides, T., Murzin, A.G., Murzina, N.V., Laue, E.D. Nature (2002) [Pubmed]
  7. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Lachner, M., O'Carroll, D., Rea, S., Mechtler, K., Jenuwein, T. Nature (2001) [Pubmed]
  8. Restricted recognition of beta 2-microglobulin by cytotoxic T lymphocytes. Rammensee, H.G., Robinson, P.J., Crisanti, A., Bevan, M.J. Nature (1986) [Pubmed]
  9. Phosphorylation of histone H3 at serine 10 is indispensable for neoplastic cell transformation. Choi, H.S., Choi, B.Y., Cho, Y.Y., Mizuno, H., Kang, B.S., Bode, A.M., Dong, Z. Cancer Res. (2005) [Pubmed]
  10. Substrate specificity and kinetic mechanism of mammalian G9a histone H3 methyltransferase. Patnaik, D., Chin, H.G., Estève, P.O., Benner, J., Jacobsen, S.E., Pradhan, S. J. Biol. Chem. (2004) [Pubmed]
  11. Expression screening of a yeast artificial chromosome contig refines the location of the mouse H3a minor histocompatibility antigen gene. Zuberi, A.R., Christianson, G.J., Dave, S.B., Bradley, J.A., Roopenian, D.C. J. Immunol. (1998) [Pubmed]
  12. A genetic linkage map of mouse chromosome 2 extending from thrombospondin to paired box gene 1, including the H3 minor histocompatibility complex. Zuberi, A.R., Nguyen, H.Q., Auman, H.J., Taylor, B.A., Roopenian, D.C. Genomics (1996) [Pubmed]
  13. A lymphocyte antigen encoded by a locus closely linked to H-3 on the second chromosome of the mouse. Gasser, D.L., Ziebur, J., Matsumoto, K. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  14. Responses against antigens encoded by the H-3 histocompatibility locus: antigens stimulating class I MHC- and class II MHC-restricted T cells are encoded by separate genes. Roopenian, D.C., Davis, A.P. Immunogenetics (1989) [Pubmed]
  15. Evidence against suppressor cell involvement in naturally acquired tolerance of a minor histocompatibility antigen. Johnson, L.L. Transplantation (1991) [Pubmed]
  16. Coupling of replication type histone mRNA levels to DNA synthesis requires the stem-loop sequence at the 3' end of the mRNA. Levine, B.J., Chodchoy, N., Marzluff, W.F., Skoultchi, A.I. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  17. Relationship between mitogenic activity of influenza viruses and the receptor-binding specificity of their hemagglutinin molecules. Anders, E.M., Scalzo, A.A., Rogers, G.N., White, D.O. J. Virol. (1986) [Pubmed]
  18. Direct role of viral hemagglutinin in B-cell mitogenesis by influenza viruses. Poumbourios, P., Anders, E.M., Scalzo, A.A., White, D.O., Hampson, A.W., Jackson, D.C. J. Virol. (1987) [Pubmed]
  19. Molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2. Peña, P.V., Davrazou, F., Shi, X., Walter, K.L., Verkhusha, V.V., Gozani, O., Zhao, R., Kutateladze, T.G. Nature (2006) [Pubmed]
  20. Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurora kinases. Crosio, C., Fimia, G.M., Loury, R., Kimura, M., Okano, Y., Zhou, H., Sen, S., Allis, C.D., Sassone-Corsi, P. Mol. Cell. Biol. (2002) [Pubmed]
  21. Sequences of four mouse histone H3 genes: implications for evolution of mouse histone genes. Taylor, J.D., Wellman, S.E., Marzluff, W.F. J. Mol. Evol. (1986) [Pubmed]
  22. Ser-10 phosphorylation of histone H3 and immediate early gene expression in oncogene-transformed mouse fibroblasts. Strelkov, I.S., Davie, J.R. Cancer Res. (2002) [Pubmed]
  23. Molecular mimicry: histone H3 and mycobacterial protein epitopes. Eriksen, N., Kumar, S.B., Fukuchi, K., Martin, G.M., Benditt, E.P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  24. CTL and serologically defined antigens of B2m,H-3 region. Kurtz, M.E., Graff, R.J., Adelman, A., Martin-Morgan, D., Click, R.E. J. Immunol. (1985) [Pubmed]
  25. Genes in mice that affect susceptibility to cortisone-induced cleft palate are closely linked to Ir genes on chromosomes 2 and 17. Gasser, D.L., Mele, L., Lees, D.D., Goldman, A.S. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  26. Evidence for linkage of murine beta 2-microglobulin to H-3 and Ly-4. Goding, J.W. J. Immunol. (1981) [Pubmed]
  27. Positional cloning and molecular characterization of an immunodominant cytotoxic determinant of the mouse H3 minor histocompatibility complex. Zuberi, A.R., Christianson, G.J., Mendoza, L.M., Shastri, N., Roopenian, D.C. Immunity (1998) [Pubmed]
  28. Probing the instabilities in the dynamics of helical fragments from mouse PrPC. Dima, R.I., Thirumalai, D. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  29. Ly-m11: the H-3 region of mouse chromosome 2 controls a new surface alloantigen. Tada, N., Kimura, S., Hatzfeld, A., Hämmerling, U. Immunogenetics (1980) [Pubmed]
  30. An immunodominant minor histocompatibility alloantigen that initiates corneal allograft rejection. Haskova, Z., Sproule, T.J., Roopenian, D.C., Ksander, A.B. Transplantation (2003) [Pubmed]
  31. Regulation of histone mRNA production and stability in serum-stimulated mouse 3T6 fibroblasts. DeLisle, A.J., Graves, R.A., Marzluff, W.F., Johnson, L.F. Mol. Cell. Biol. (1983) [Pubmed]
  32. Enhancement of Sleeping Beauty transposition by CpG methylation: possible role of heterochromatin formation. Yusa, K., Takeda, J., Horie, K. Mol. Cell. Biol. (2004) [Pubmed]
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