RESUMO
Sex chromosomes in different organisms are studied as model systems for chromatin regulation of transcription and epigenetics. Similar to the female X in mammals, the male X chromosome in Drosophila is involved in the process of dosage compensation. However, in contrast to one of the mammalian female X chromosomes undergoing inactivation, the Drosophila male X is transcriptionally upregulated by approximately twofold. The Drosophila male X is a remarkable example for a specialized, transcriptionally hyperactive chromatin domain that facilitates the study of chromatin regulation in the context of transcription, nuclear architecture, and chromatin remodeling. In addition, the rich phenomenology of dosage compensation in Drosophila provides an opportunity to explore the complexities of gene regulation through epigenetic chromatin configurations, histone modifications, and noncoding RNAs. Male-specific lethal (MSL) factors constitute the MSL complex or dosage compensation complex and are important for transcription regulation of X-linked genes. Recent biochemical studies have identified a number of interesting factors that associate with the MSL complex including components of the nuclear pore complex and exosome subunits. Furthermore, global analysis of MSL complex binding showed that MSL complexes are enriched on genes with preferential binding to 3' end of genes. Taken together, these findings suggest a role of the MSL complex in transcription elongation, RNA processing, and/or nuclear organization.
Assuntos
Cromatina/metabolismo , Mecanismo Genético de Compensação de Dose/genética , Drosophila/genética , Epigênese Genética , Regulação da Expressão Gênica , Modelos Genéticos , Complexos Multiproteicos/metabolismo , Cromossomo X/genética , Animais , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , DNA Helicases/genética , DNA Helicases/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Masculino , Complexos Multiproteicos/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Dosage compensation in Drosophila is dependent on MSL proteins and involves hypertranscription of the male X chromosome, which ensures equal X-linked gene expression in both sexes. Here, we report the purification of enzymatically active MSL complexes from Drosophila embryos, Schneider cells, and human HeLa cells. We find a stable association of the histone H4 lysine 16-specific acetyltransferase MOF with the RNA/protein containing MSL complex as well as with an evolutionary conserved complex. We show that the MSL complex interacts with several components of the nuclear pore, in particular Mtor/TPR and Nup153. Strikingly, knockdown of Mtor or Nup153 results in loss of the typical MSL X-chromosomal staining and dosage compensation in Drosophila male cells but not in female cells. These results reveal an unexpected physical and functional connection between nuclear pore components and chromatin regulation through MSL proteins, highlighting the role of nucleoporins in gene regulation in higher eukaryotes.
