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1.
Nat Genet ; 50(8): 1102-1111, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29967444

RESUMO

The koala, the only extant species of the marsupial family Phascolarctidae, is classified as 'vulnerable' due to habitat loss and widespread disease. We sequenced the koala genome, producing a complete and contiguous marsupial reference genome, including centromeres. We reveal that the koala's ability to detoxify eucalypt foliage may be due to expansions within a cytochrome P450 gene family, and its ability to smell, taste and moderate ingestion of plant secondary metabolites may be due to expansions in the vomeronasal and taste receptors. We characterized novel lactation proteins that protect young in the pouch and annotated immune genes important for response to chlamydial disease. Historical demography showed a substantial population crash coincident with the decline of Australian megafauna, while contemporary populations had biogeographic boundaries and increased inbreeding in populations affected by historic translocations. We identified genetically diverse populations that require habitat corridors and instituting of translocation programs to aid the koala's survival in the wild.


Assuntos
Adaptação Fisiológica/genética , Phascolarctidae/genética , Animais , Austrália , Infecções por Chlamydia/genética , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Genoma , Anotação de Sequência Molecular/métodos , Phascolarctidae/metabolismo , Translocação Genética
2.
Prog Mol Subcell Biol ; 56: 257-281, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28840241

RESUMO

The chromosome biology field at large has benefited from studies of the cell cycle components, protein cascades and genomic landscape that are required for centromere identity, assembly and stable transgenerational inheritance. Research over the past 20 years has challenged the classical descriptions of a centromere as a stable, unmutable, and transcriptionally silent chromosome component. Instead, based on studies from a broad range of eukaryotic species, including yeast, fungi, plants, and animals, the centromere has been redefined as one of the more dynamic areas of the eukaryotic genome, requiring coordination of protein complex assembly, chromatin assembly, and transcriptional activity in a cell cycle specific manner. What has emerged from more recent studies is the realization that the transcription of specific types of nucleic acids is a key process in defining centromere integrity and function. To illustrate the transcriptional landscape of centromeres across eukaryotes, we focus this review on how transcripts interact with centromere proteins, when in the cell cycle centromeric transcription occurs, and what types of sequences are being transcribed. Utilizing data from broadly different organisms, a picture emerges that places centromeric transcription as an integral component of centromere function.


Assuntos
Centrômero/genética , Transcrição Gênica , Animais , Ciclo Celular/genética , Cromatina/genética , Montagem e Desmontagem da Cromatina/genética
3.
Elife ; 62017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28760200

RESUMO

Heterochromatin formed by the SUV39 histone methyltransferases represses transcription from repetitive DNA sequences and ensures genomic stability. How SUV39 enzymes localize to their target genomic loci remains unclear. Here, we demonstrate that chromatin-associated RNA contributes to the stable association of SUV39H1 with constitutive heterochromatin in human cells. We find that RNA associated with mitotic chromosomes is concentrated at pericentric heterochromatin, and is encoded, in part, by repetitive α-satellite sequences, which are retained in cis at their transcription sites. Purified SUV39H1 directly binds nucleic acids through its chromodomain; and in cells, SUV39H1 associates with α-satellite RNA transcripts. Furthermore, nucleic acid binding mutants destabilize the association of SUV39H1 with chromatin in mitotic and interphase cells - effects that can be recapitulated by RNase treatment or RNA polymerase inhibition - and cause defects in heterochromatin function. Collectively, our findings uncover a previously unrealized function for chromatin-associated RNA in regulating constitutive heterochromatin in human cells.


Assuntos
Heterocromatina/metabolismo , Metiltransferases/metabolismo , RNA/metabolismo , Proteínas Repressoras/metabolismo , Linhagem Celular , Humanos , Ligação Proteica
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