RESUMEN
Countries must learn how to capitalize on their citizens' cognitive resources if they are to prosper, both economically and socially. Early interventions will be key.
Asunto(s)
Trastornos Mentales/economía , Salud Mental , Adolescente , Adulto , Anciano de 80 o más Años , Envejecimiento/psicología , Niño , Desarrollo Infantil , Costo de Enfermedad , Depresión/economía , Humanos , Discapacidades para el Aprendizaje/economía , Trastornos Mentales/prevención & control , Trastornos Mentales/psicología , Factores de Riesgo , Reino Unido , Trabajo/psicologíaRESUMEN
RNA polymerase (Pol) I-transcribed ribosomal genes of budding yeast exist as a tandem array (about 150 repeats) with transcription units separated by spacer sequences. Half of these rDNAs are inactivated by repressive chromatin structure, whereas the rest exist in an open conformation transcribed by closely spaced Pol I elongation complexes. Whereas previous studies have suggested that active rDNA is devoid of nucleosomal structure, we demonstrate that active rDNA has nucleosomal structure, according to chromatin immunoprecipitation and biochemical fractionation. Using a yeast strain with reduced numbers of all actively transcribed rDNA repeats, we show that rDNA exists in a dynamic chromatin structure of unphased nucleosomes. Furthermore, it is associated with chromatin-remodeling enzymes Chd1p, Isw1p and Isw2p, whose inactivation causes defects in transcription termination. We suggest that Pol I transcription, like that of Pol II, may be modulated by specific chromatin structures.
Asunto(s)
ADN de Hongos/genética , ADN Ribosómico/genética , Nucleosomas/genética , ARN Polimerasa I/genética , Saccharomyces cerevisiae/genética , Adenosina Trifosfatasas/metabolismo , Cromatina/genética , Cromatina/metabolismo , ADN de Hongos/metabolismo , ADN Ribosómico/metabolismo , Proteínas de Unión al ADN/metabolismo , Inmunoprecipitación , Nucleosomas/metabolismo , ARN Polimerasa I/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Factores de Transcripción/metabolismo , Transcripción GenéticaRESUMEN
Chromatin remodeling can facilitate the recruitment of RNA polymerase II (Pol II) to targeted promoters, as well as enhancing the level of transcription. Here, we describe a further key role for chromatin remodeling in transcriptional termination. Using a genetic screen in S. pombe, we identified the CHD-Mi2 class chromatin remodeling ATPase, Hrp1, as a termination factor. In S. cerevisiae, we show that transcriptional termination and chromatin structure at the 3' ends of three genes all depend on the activity of the Hrp1 homolog, Chd1p, either alone or redundantly with the ISWI ATPases, Isw1p, and Isw2p. We suggest that chromatin remodeling of termination regions is a necessary prelude to efficient Pol II termination.
Asunto(s)
Cromatina/ultraestructura , Regulación Fúngica de la Expresión Génica , ARN Polimerasa II/metabolismo , Schizosaccharomyces/genética , Transcripción Genética , Regiones no Traducidas 3'/genética , Sitios de Unión , Cromatina/genética , ADN de Hongos/genética , ADN de Hongos/metabolismo , Regulación Enzimológica de la Expresión Génica , Nucleasa Microcócica/metabolismo , ARN Polimerasa II/genética , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/genética , Schizosaccharomyces/enzimologíaRESUMEN
We identify Rpa12p of RNA polymerase I (Pol I) as a termination factor. Combined analyses using transcription run-on, electron microscopy-visualized chromatin spreading and RT-PCR have been applied to the rRNA-encoding genes of Saccharomyces cerevisiae. These confirm that Pol I termination occurs close to the Reb1p-dependent terminator in wild-type strains. However, deletion mutants for the 3' end-processing enzyme Rnt1p or the Rpa12p subunit of Pol I both show Pol I transcription in the spacer. For Deltarpa12, these spacer polymerases are devoid of nascent transcripts, suggesting they are immediately degraded. The homology of Rpa12p to the small subunit Rpb9p of Pol II and Rpc11p of Pol III, both implicated in transcriptional termination, points to a common termination mechanism for all three classes of RNA polymerase.