No abstract

a b s t r a c tThe identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology.

The initiation of chromosome morphogenesis marks the beginning of mitosis in all eukaryotic cells. Although many effectors of chromatin compaction have been reported, the nature and design of the essential trigger for global chromosome assembly remain unknown. Here we reveal the identity of the core mechanism responsible for chromosome morphogenesis in early mitosis. We show that the unique sensitivity of the chromosome condensation machinery for the kinase activity of Cdk1 acts as a major driving force for the compaction of chromatin at mitotic entry. This sensitivity is imparted by multisite phosphorylation of a conserved chromatinbinding sensor, the Smc4 protein. The multisite phosphorylation of this sensor integrates the activation state of Cdk1 with the dynamic binding of the condensation machinery to chromatin. Abrogation of this event leads to chromosome segregation defects and lethality, while moderate reduction reveals the existence of a novel chromatin transition state specific to mitosis, the intertwist configuration. Collectively, our results identify the mechanistic basis governing chromosome morphogenesis in early mitosis and how distinct chromatin compaction states can be established via specific thresholds of Cdk1 kinase activity.

Condensins associate with DNA and shape mitotic chromosomes. Condensins are enriched nearby highly expressed genes during mitosis, but how this binding is achieved and what features associated with transcription attract condensins remain unclear. Here, we report that condensin accumulates at or in the immediate vicinity of nucleosome-depleted regions during fission yeast mitosis. Two transcriptional coactivators, the Gcn5 histone acetyltransferase and the RSC chromatin-remodelling complex, bind to promoters adjoining condensin-binding sites and locally evict nucleosomes to facilitate condensin binding and allow efficient mitotic chromosome condensation. The function of Gcn5 is closely linked to condensin positioning, since neither the localization of topoisomerase II nor that of the cohesin loader Mis4 is altered in gcn5 mutant cells. We propose that nucleosomes act as a barrier for the initial binding of condensin and that nucleosome-depleted regions formed at highly expressed genes by transcriptional coactivators constitute access points into chromosomes where condensin binds free genomic DNA.