RESUMEN
Centromeres represent the basis for kinetochore formation, and are essential for proper chromosome segregation during mitosis. Despite these essential roles, centromeres are not defined by specific DNA sequences, but by epigenetic means. The histone variant CENP-A controls centromere identity epigenetically and is essential for recruiting kinetochore components that attach the chromosomes to the mitotic spindle during mitosis. Recently, a new player in centromere regulation has emerged: long non-coding RNAs transcribed from repetitive regions of centromeric DNA function in regulating centromeres epigenetically. This review summarizes recent findings on the essential roles that transcription, pericentromeric transcripts, and centromere-derived RNAs play in centromere biology.
Asunto(s)
Autoantígenos/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Epigenómica , ARN Largo no Codificante/metabolismo , Centrómero/metabolismo , Proteína A Centromérica , Cromatina/metabolismo , Humanos , Cinetocoros , MitosisRESUMEN
Methylation at the 5 position of cytosine in DNA (5meC) is a key epigenetic mark in eukaryotes. Once introduced, 5meC can be maintained through DNA replication by the activity of 'maintenance' DNA methyltransferases (DNMTs). Despite their ancient origin, DNA methylation pathways differ widely across animals, such that 5meC is either confined to transcribed genes or lost altogether in several lineages. We used comparative epigenomics to investigate the evolution of DNA methylation. Although the model nematode Caenorhabditis elegans lacks DNA methylation, more basal nematodes retain cytosine DNA methylation, which is targeted to repeat loci. We found that DNA methylation coevolved with the DNA alkylation repair enzyme ALKB2 across eukaryotes. In addition, we found that DNMTs introduced the toxic lesion 3-methylcytosine into DNA both in vitro and in vivo. Alkylation damage is therefore intrinsically associated with DNMT activity, and this may promote the loss of DNA methylation in many species.
Asunto(s)
ADN (Citosina-5-)-Metiltransferasas/metabolismo , Daño del ADN , Metilación de ADN/fisiología , Evolución Molecular , Animales , Caenorhabditis elegans , Secuencia Conservada , Elementos Transponibles de ADN/fisiología , Eucariontes/clasificación , Eucariontes/genética , Humanos , Mermithoidea , Ratones , Ratones SCID , Nematodos/clasificación , Nematodos/genética , Filogenia , Alineación de Secuencia , Análisis de Secuencia de Proteína , TrichurisRESUMEN
The amphipod crustacean Parhyale hawaiensis is a blossoming model system for studies of developmental mechanisms and more recently regeneration. We have sequenced the genome allowing annotation of all key signaling pathways, transcription factors, and non-coding RNAs that will enhance ongoing functional studies. Parhyale is a member of the Malacostraca clade, which includes crustacean food crop species. We analysed the immunity related genes of Parhyale as an important comparative system for these species, where immunity related aquaculture problems have increased as farming has intensified. We also find that Parhyale and other species within Multicrustacea contain the enzyme sets necessary to perform lignocellulose digestion ('wood eating'), suggesting this ability may predate the diversification of this lineage. Our data provide an essential resource for further development of Parhyale as an experimental model. The first malacostracan genome will underpin ongoing comparative work in food crop species and research investigating lignocellulose as an energy source.
Asunto(s)
Anfípodos/genética , Proteínas de Artrópodos/genética , Genoma , Estadios del Ciclo de Vida/genética , Lignina/metabolismo , Redes y Vías Metabólicas/genética , Anfípodos/clasificación , Anfípodos/crecimiento & desarrollo , Anfípodos/metabolismo , Animales , Acuicultura , Proteínas de Artrópodos/inmunología , Femenino , Regulación del Desarrollo de la Expresión Génica , Ontología de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Inmunidad Innata , Cariotipo , Estadios del Ciclo de Vida/inmunología , Masculino , Redes y Vías Metabólicas/inmunología , Anotación de Secuencia Molecular , Filogenia , ARN no Traducido/genética , ARN no Traducido/inmunología , Regeneración , Transducción de Señal , Factores de Transcripción/genética , Factores de Transcripción/inmunologíaRESUMEN
Chromosome segregation requires centromeres on every sister chromatid to correctly form and attach the microtubule spindle during cell division. Even though centromeres are essential for genome stability, the underlying centromeric DNA is highly variable in sequence and evolves quickly. Epigenetic mechanisms are therefore thought to regulate centromeres. Here, we show that the 359-bp repeat satellite III (SAT III), which spans megabases on the X chromosome of Drosophila melanogaster, produces a long noncoding RNA that localizes to centromeric regions of all major chromosomes. Depletion of SAT III RNA causes mitotic defects, not only of the sex chromosome but also in trans of all autosomes. We furthermore find that SAT III RNA binds to the kinetochore component CENP-C, and is required for correct localization of the centromere-defining proteins CENP-A and CENP-C, as well as outer kinetochore proteins. In conclusion, our data reveal that SAT III RNA is an integral part of centromere identity, adding RNA to the complex epigenetic mark at centromeres in flies.