Form and function of topologically associating genomic domains in budding yeast.
Proc Natl Acad Sci U S A
; 114(15): E3061-E3070, 2017 04 11.
Article
em En
| MEDLINE
| ID: mdl-28348222
ABSTRACT
The genome of metazoan cells is organized into topologically associating domains (TADs) that have similar histone modifications, transcription level, and DNA replication timing. Although similar structures appear to be conserved in fission yeast, computational modeling and analysis of high-throughput chromosome conformation capture (Hi-C) data have been used to argue that the small, highly constrained budding yeast chromosomes could not have these structures. In contrast, herein we analyze Hi-C data for budding yeast and identify 200-kb scale TADs, whose boundaries are enriched for transcriptional activity. Furthermore, these boundaries separate regions of similarly timed replication origins connecting the long-known effect of genomic context on replication timing to genome architecture. To investigate the molecular basis of TAD formation, we performed Hi-C experiments on cells depleted for the Forkhead transcription factors, Fkh1 and Fkh2, previously associated with replication timing. Forkhead factors do not regulate TAD formation, but do promote longer-range genomic interactions and control interactions between origins near the centromere. Thus, our work defines spatial organization within the budding yeast nucleus, demonstrates the conserved role of genome architecture in regulating DNA replication, and identifies a molecular mechanism specifically regulating interactions between pericentric origins.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromatina
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Genoma Fúngico
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Genômica
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Proteínas de Saccharomyces cerevisiae
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Saccharomycetales
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2017
Tipo de documento:
Article