Mammalian histone variant H3.3 differs from replication-dependent histone H3.1 by five amino acids, including replacement of alanine 31 by serine. H3.3 is expressed throughout the cell cycle, primarily deposited at transcriptionally active loci independent of S-phase. Data from mammalian cells suggest that phosphorylation of serine 31 (H3.3S31P) plays a role in mitosis. Here we show that H3.3S31P also occurs during mitosis of the urochordate Oikopleura dioica, suggesting this histone modification and its function in mitosis is already present at the invertebrate-vertebrate transition. The spatial pattern differed from that of H3 phosphorylation at serine 28 (H3S28P). H3S28P was enriched near telomeric regions, but H3.3S31P differed both temporally and spatially from the mammalian pattern, being more widely distributed throughout prophase, prometaphase and metaphase chromosomes. We also identified an important role for H3.3S31P during oogenic meiosis in the semelparous O. dioica. H3.3S31P initiated together with H3S28P in all meiotic nuclei in late diplotene, after H3S10P. However, H3.3S31P was retained only on the subset of meiotic nuclei that seeded maturing oocytes and proceeded through meiosis to arrest in metaphase I. Thus, this epigenetic mark is part of a regulatory circuitry that enables O. dioica to numerically adjust oocyte production over two orders of magnitude.
Humoral immune reactions to heat shock proteins (hsp) from microorganisms are one aspect of microbial infections in humans. The production of antibodies which are specific to epitopes present on procaryotic hsp leads also to the appearance of cross-reactive serum antibodies in the host organism that react with human hsp. This article discusses the consequences of such autoreactive antibodies for the host in context with the development of immune tolerance and autoimmune diseases, especially rheumatoid arthritis (RA), and in experimental animal models for arthritis such as adjuvant arthritis in rats. On the basis of epitope cross-reactivity between hsp and other host proteins, a hypothesis is presented for the development of autoimmune disease following the production of hsp-specific antibodies.
The autoantigen in adjuvant arthritis in Lewis rats is still unknown despite the knowledge that the 65 kDa mycobacterial heat-shock protein (hsp) is involved in the disease process. T cells and antibodies obtained from rats with adjuvant arthritis respond to chondrocyte membrane antigen(s). In Western blots a 65 kDa chondrocyte membrane protein (CH65) is stained by sera from arthritic rats. In addition, spleen cells from rats with adjuvant arthritis proliferate in vitro to chondrocyte membranes and CH65 as antigens. Furthermore, pretreatment of rats with CH65 or mycobacterial hsp65 but not human hsp60, induces a significant retardation of the onset of adjuvant arthritis in Lewis rats. The data suggest that CH65 is a potential autoantigen involved in the pathogenesis of adjuvant arthritis in Lewis rats.
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