RESUMEN
In both mammalian and Drosophila spermatids, the completely histone-based chromatin structure is reorganized to a largely protamine-based structure. During this histone-to-protamine switch, transition proteins are expressed, for example TNP1 and TNP2 in mammals and Tpl94D in Drosophila. Recently, we demonstrated that in Drosophila spermatids, H3K79 methylation accompanies histone H4 hyperacetylation during chromatin reorganization. Preceding the histone-to-protamine transition, the H3K79 methyltransferase Grappa is expressed, and the predominant isoform bears a C-terminal extension. Here, we show that isoforms of the Grappa-equivalent protein in humans, rats and mice, that is DOT1L, have a C-terminal extension. In mice, the transcript of this isoform was enriched in the post-meiotic stages of spermatogenesis. In human and mice spermatids, di- and tri-methylated H3K79 temporally overlapped with hyperacetylated H4 and thus accompanied chromatin reorganization. In rat spermatids, trimethylated H3K79 directly preceded transition protein loading on chromatin. We analysed the impact of bacterial infections on spermatid chromatin using a uropathogenic Escherichia coli-elicited epididymo-orchitis rat model and showed that these infections caused aberrant spermatid chromatin. Bacterial infections led to premature emergence of trimethylated H3K79 and hyperacetylated H4. Trimethylated H3K79 and hyperacetylated H4 simultaneously occurred with transition protein TNP1, which was never observed in spermatids of mock-infected rats. Upon bacterial infection, only histone-based spermatid chromatin showed abnormalities, whereas protamine-compacted chromatin seemed to be unaffected. Our results indicated that H3K79 methylation is a histone modification conserved in Drosophila, mouse, rat and human spermatids and may be a prerequisite for proper chromatin reorganization.
Asunto(s)
Ensamble y Desensamble de Cromatina/fisiología , Histonas/metabolismo , Espermátides/citología , Espermátides/microbiología , Espermatogénesis/fisiología , Acetilación , Animales , Diferenciación Celular , Proteínas Cromosómicas no Histona/metabolismo , Drosophila melanogaster , Epididimitis/microbiología , Escherichia coli/patogenicidad , Infecciones por Escherichia coli , N-Metiltransferasa de Histona-Lisina , Humanos , Masculino , Metilación , Metiltransferasas/genética , Ratones , Ratones Endogámicos C57BL , Orquitis/microbiología , Protaminas/metabolismo , Isoformas de Proteínas/genética , Ratas , Testículo/metabolismoRESUMEN
Giant multicentric hyperplasia of the lymph nodes (GMHLN) is currently regarded as a disseminated form of angiofollicular lymphoid hyperplasia, or Castleman's disease. An immunologic study was carried out on a 24 year-old Caucasian woman who was admitted to hospital with generalised lymph node enlargement, jaundice and fever, and showed an excellent response to steroid therapy. No alterations were found in the lymphocytic subsets, the intrinsic B cell function or the T-B cooperative capability. These data disagree with the hypothesis than GMHLN is due to a deficiency of the T cell suppressive function with concomitant immunoglobulin over-production.